Assembly of functionally integrated human forebrain spheroids.
- Authors
- Birey, Fikri; Andersen, Jimena; Makinson, Christopher D; Islam, Saiful; Wei, Wu; Huber, Nina; Fan, H Christina; Metzler, Kimberly R Cordes; Panagiotakos, Georgia; Thom, Nicholas; O'Rourke, Nancy A; Steinmetz, Lars M; Bernstein, Jonathan A; Hallmayer, Joachim; Huguenard, John R; PaΕca, Sergiu P
- Year
- 2017
- Journal
- Nature
- PMID
- 28445465
- DOI
- 10.1038/nature22330
- PMCID
- PMC5805137
The development of the nervous system involves a coordinated succession of events including the migration of GABAergic (Ξ³-aminobutyric-acid-releasing) neurons from ventral to dorsal forebrain and their integration into cortical circuits. However, these interregional interactions have not yet been modelled with human cells. Here we generate three-dimensional spheroids from human pluripotent stem cells that resemble either the dorsal or ventral forebrain and contain cortical glutamatergic or GABAergic neurons. These subdomain-specific forebrain spheroids can be assembled in vitro to recapitulate the saltatory migration of interneurons observed in the fetal forebrain. Using this system, we find that in Timothy syndrome-a neurodevelopmental disorder that is caused by mutations in the Ca1.2 calcium channel-interneurons display abnormal migratory saltations. We also show that after migration, interneurons functionally integrate with glutamatergic neurons to form a microphysiological system. We anticipate that this approach will be useful for studying neural development and disease, and for deriving spheroids that resemble other brain regions to assemble circuits in vitro.
Immunostaining of hSS in cryosections showing PV neuronsTwo antiβPV antibodies have been used to validate specificity; co-localization with the neuronal marker DCX (day 209).
Characterization of Dlxi1/2b::eGFP+ cells after migration(a) Representative images of 3Dβreconstructed Dlxi1/2b::eGFP+ cell morphologies before and after migration from hSS into hCS. (b) Quantification of dendritic branching of Dlxi1/2b::eGFP+ cells in hSS (n= 58 cells) and in hCS (n= 55 cells) of fused hSS-hCS (two-way ANOVA; interaction F(2, 129)= 11.29, P< 0.001; Bonferroni post-hoc *P< 0.05, ***P< 0.001). (c) Representative examples of action potentials (slice recordings) in Dlxi1/2b::eGFP+ cells in unfused hSS, in hSS of fused hSS-hCS and in hCS after migration in fused hSS-hCS. (d) AT showing expression of the GABAergic synapse marker GPHN (green) colocalized with SYN1 (red) in hCS of fused hSS-hCS but not in unfused hCS; the glutamatergic marker PSD95 (cyan) colocalized with SYN1 is found in both fused and unfused hCS (equal volumes 1.2 ΞΌm deep). (e) AT of a Dlxi1/2b::eGFP+ synapse illustrating the colocalization with SYN1 (red), GPHN (cyan), and VGAT (white); 5 consecutive 70 nm sections (3 Γ 3 ΞΌm). (f) Representative examples of whole-cell voltage clamp recordings of IPSCs and EPSCs from Dlxi1/2b::eGFP+ cells in unfused hSS, in fused hCS-hSS, or after migration in hCS (g) Representative examples of whole-cell voltage clamp recordings of IPSCs and EPSCs in cells recorded from unfused hCS cells and fused hCS cells. (h) Electrical stimulation and patch clamp recording in fused hSS-hCS showing evoked EPSCs and IPSCs before (black) and after exposure to 10 ΞΌM gabazine (red). (i) Average peri-stimulus synaptic events (IPSCs and EPSCs) in Dlxi1/2::eGFP+ cells recorded in the hCS side of fused hSS-hCS before and after electrical stimulation (paired t-test, *P< 0.05). Data are mean Β± s.e.m.
Characterization of hSS derived from hPSC(a) Generation of hCS and hSS. (b) Fold changes (relative to gene expression in hPSC; normalized to GAPDH) of NKX2β1 (n= 6 hPSC lines; Mann-Whitney test, P= 0.002), FOXG1 (n= 5 hPSC lines; t-test, P= 0.35) and EMX1 (n= 4 hPSC lines; Mann-Whitney test, P= 0.02) in hCS and hSS at day 25. (c, d) Immunostaining of hSS for NKX2β1, (e, f) GABA, GAD67 and MAP2, and (g, h) SST, CR, CB, PV. (i, j) Single cell profiling of hCS and hSS. (k) AT volume in hSS for MAP2, GFAP, SYN1 and VGAT. (l) Patch clamping in sliced hSS and a representative trace of whole-cell current-clamp recording. (m, n) Spontaneous IPSCs before (black) and during (blue) application of gabazine in an hSS slice (paired t-test, **P= 0.004).
Cell migration in fused hSS-hCS(a) Assembly of hCS and hSS. (b) Morphology before and after assembly. (c) Time-lapse of migration from hSS into hCS. (d) Assembly of hCS (AAV-hSYN1::mCherry) and hSS (Lenti-Dlxi1/2b::eGFP). (e) iDISCO-cleared hSS-hCS. (f, g) Saltatory migration of Dlxi1/2b::eGFP+ cells in fused hSS-hCS and (h) nucleokinesis. (I, j) Saltatory migration of Dlxi1/2b::eGFP+ cells in human fetal forebrain and (k) nucleokinesis.
Modeling of interneuron migration in hSS-hCS derived from Timothy syndrome(a) TS mutation in Cav1.2. (b) Calcium imaging in dissociated hSS (Ctrl: n= 38 cells from 2 subjects; TS: n= 68 cells from 2 subjects). (c) Migration of Dlxi1/2b::eGFP+ cells in TS and control hSS-hCS. (d, e) Number of saltations (Ctrl: n= 48 cells from 3 hiPSC lines derived from 3 subjects; TS: n= 51 cells from 3 hiPSC lines derived from 3 subjects; TS-Ctrl hybrid: n= 24 cells from 5 hiPSC line combinations from 2 TS and 2 Ctrl subjects), and saltation length (Ctrl: n= 21 cells from 3 hiPSC lines derived from 3 subjects; TS: n= 29 cells from 3 hiPSC derived from 3 subjects; TS-Ctrl hybrid: n= 12 cells from 3 hiPSC line combinations from 2 TS and 3 Ctrl subjects); one-way ANOVA with Dunnettβs multiple comparison test (***, P< 0.001). (f) Migration of TS and control Dlxi1/2b::eGFP+ cells in fused hSS-hCS (two-way ANOVA, interaction F(24, 408)= 17.71, P< 0.0001). (g) Saltation length following exposure to nimodipine (paired t-test; Ctrl: n= 13 cells from 3 hiPSC lines derived from 3 subjects, ***P< 0.001; TS: n= 12 cells from 2 hiPSC lines derived from 2 subjects, ***P< 0.001).
Functional integration of interneurons in fused hSS-hCS(a) Isolation of Dlxi1/2b::eGFP+ cells for transcriptional analysis. (b) t-SNE visualization of single cell gene expression at day 121 (4 weeks after hSS-hCS assembly). (c) Distribution across clusters (Ο2-test, Ο2= 43.39, P< 0.0001). (d) Expression of ERBB4, NXPH1, IGF1, TCF4, FOS, RAD1. (e) Morphology of Dlxi1/2b::eGFP+ cells before and after migration into hCS (f) Action potential generation in Dlxi1/2b::eGFP+ cells (one-way ANOVA, F(2, 30)= 1.25; ***P< 0.001; Bonferroni post-hoc, **P< 0.01; ***P< 0.001). (g) GABAergic synapse (by AT) on the pallial side of hCS-hSS with SYN1, GPHN and VGAT. (h) EPSCs and IPSCs in Dlxi1/2b::eGFP+ cells after migration. (i) Synaptic responses in Dlxi1/2b::eGFP+ cells (two-way ANOVA, interaction F(2, 61)= 18.46, P< 0.0001; Bonferroni post-hoc for EPSCs, ***P< 0.0001, **P< 0.001). (j) Synaptic responses in excitatory cells (two-way ANOVA, cortical neurons in hCS before and after assembly F(1, 26)= 5.6, P< 0.05; Bonferroni post-hoc for IPSC, *P< 0.05).
Single cell gene expression of hCS and hSS at day 105 of differentiation (n= 11,838 cells; BD Resolve system)(a) Distribution of expression of the neuronal marker STMN2, (b) the progenitor marker VIM and of (c) a set of genes associated with the M cell cycle phase (AURKB, TPX2, UBE2C, HMMR, TOP2A, CCNB1, NUSAP1, NUF2, CDC6, HIST1H4C, BIRC5, CKS2). (d) Boxplots for genes enriched in each t-SNE cluster shown in Fig. 1j. (eβl) Top 25 genes in each of the 8 clusters shown in Fig. 1j (proportion of molecules per cells). (m) Scatter plot showing the number of genes detected versus the number of useful reads.
Characterization of hSS differentiation conditions(a) Schematic illustrating the differentiation conditions for deriving hCS or hSS: IS, ISA and and ISRA. (b) Representative traces of intracellular calcium measurements (Fluo-4) demonstrating spontaneous activity in hSS at ~day 50 of differentiation. (c) Average calcium spike frequency in 3 distinct hSS differentiation conditions: IS (n= 114 cells), ISA (n= 327 cells), ISRA (n= 136 cells); cells derived from 3 hiPSC lines; one-way ANOVA, F(3, 719)= 5.86, ***P< 0.001. (d) Gene expression (qPCR, normalized to GAPDH) showing down-regulation of OCT4 and the lack of mesoderm (BRACH) and endoderm (SOX17) markers following differentiation of hiPSC into hCS and hSS conditions. (e) Gene expression (qPCR, fold change versus hiPSC and normalized to GAPDH) showing upregulation of forebrain markers (SIX3, FOXG1) but not midbrain (LMX1B), hypothalamus (RAX1) or spinal cord (HOXB4) markers. (f) Expression of ventral forebrain genes in hSS and hCS (qPCR, normalized to GAPDH) at day 25. (g) Average percentage of the proportion of NKX2β1 by immunostaining in dissociated hCS or hSS at day 25. (h) Expression of ventral forebrain genes in hSS (qPCR, normalized to GAPDH) at day 60. (i) Expression of glutamatergic, GABAergic, dopaminergic and cholinergic neurotransmitter identify genes in hSS (qPCR, normalized to GAPDH) at day 60. (j) Average percentage of the proportion of MAP2/Hoechst and GAD67/MAP2 by immunostaining in dissociated hSS at day 60. (k, l) Expression of interneuron subtypes genes and markers associated with interneuron migration in hSS (qPCR, normalized to GAPDH) at day 60. Number of lines hiPSC used indicated on each column. Data are mean Β± s.e.m.
Electrophysiological recordings of hCS and hSS(a) Representative EPSC traces of recordings from hCS neurons (sliced preparation) before (black) and during (green) exposure to the glutamate receptor blocker kynurenic acid (1 mM) (Mann-Whitney U-test, **P= 0.007). (b) Overlap of averaged EPSCs (red) recorded in hCS neurons (n= 6 cells) and averaged IPSCs (black) recorded in hSS (n= 5 cells). Data are mean Β± s.d.
Migration of Dlxi1/2::eGFP+ cells in fused hSS-hCS(a, b) Representative immunostaining in cryosections of hSS showing co-expression of Dlxi1/2::eGFP and GAD67 and GABA. (c) Quantification by immunostaining of the proportion of Dlxi1/2::eGFP+ cells that co-express GAD67 in hSS derived using the ISA or ISRA condition (n= 3 hiPSC lines; t-test, P= 0.35). (d) Proportion of Dlxi1/2::eGFP and GAD67 positive cells in hSS derived using the ISA or ISRA condition that co-express SST (t-test, P= 0.48), CR (t-test, *P= 0.04) or CB (t-test, P= 0.43); n = 3 hiPSC lines. (e) Representative images of hSS-hCS at day 60 showing migration of Dlxi1/2b::eGFP+ cells (from fluorescently labeled hSS) in fused hSS-hCS but not in hSS-hSS over time. (f) The number of Dlxi1/2b::eGFP+ (hSS-derived) or hSYN1::mCherry cells (hCS-derived) that moved in hSS-hCS or hSS-hSS was quantified in snapshots of live, intact spheroids at different time points (from day 3 to 25). The values shown are absolute number of cells that migrated to the other side (approximately the same area and thickness was imaged in each session); one-way ANOVA for cells at 17 days after assembly; F(2, 32)= 8.24, P= 0.001. (g) Representative images of fused hSS-hCS at day 91 showing migration of Dlxi1/2b::eGFP+ cells (from fluorescently labeled hSS) into fused hSS-hCS. (h) Representative image of an hSS that was plated on a glass coverslip and cultured for ~7 days. (i) Percentage of Dlxi1/2::eGFP inside the coverslip-plated hSS, in the rim (0β200 ΞΌm) or beyond this region (> 200 ΞΌm). (j) Quantification of the number of saltations of Dlxi1/2b::eGFP+ cells (n= 32 cells) inside the one-week coverslip-plated hSS, in the rim and outside this region (one-way ANOVA, interaction F (2, 30)= 22.12, P< 0.001; Bonferroni post-hoc ***P< 0.0001). (k) Diagram showing the angle of movement of migrating Dlxi1/2b::eGFP+ cells at 8β9 days after assembly of hSS-hCS. The angle was calculated between the leading process of Dlxi1/2b::eGFP+ cells that have moved into hCS and the fusion interface (n= 92 cells from 5 hiPSC lines). (l) Histogram showing the distribution of the distance of migrated Dlxi1/2b::eGFP+ cells relative to the edge of hCS in hSS-hCS at 30β50 days after assembly. The distance was measured in fixed 18 ΞΌm cryosections (n= 73 cells from 2 hiPSC lines). (m, n, o) Representative examples of Dlxi1/2b::eGFP+ cells migrated in the hCS that moved within a VZ-like region. The VZ-like region contains GFAP-expressing cells, is surrounded by TBR1+ cells and the migrated cells show GABA expression. Supplementary Video 2 shows movement of Dlxi1/2b::eGFP+ cells that is reminiscent of the ventricular-directed migration described in rodents.
Single cell gene expression of Dlxi1/2b::eGFP+ cells in hSS and hCS (Smart-seq2)(a) Scheme showing the isolation by dissociation and fluorescence-activated cell sorting (FACS) of Dlxi1/2b::eGFP+ cells from hSS or hCS for single cell transcriptional analysis. (b) Violin plots showing expression in Dlxi1/2b::eGFP+ cells of selected genes associated with cortical, striatal and olfactory interneurons in hSS (light green, n= 123 cells) or hCS (dark green; n= 106 cells) at 2 weeks after assembly of hSS-hCS. (c) Violin plots showing expression in Dlxi1/2b::eGFP+ cells (at 4 weeks after assembly of hSS-hCS) in clusters A, B, and C (likelihood ratio test; GAD1, CELF4: P> 0.05; PBX3: P< eβ7 for A versus B & C; NNAT: P< eβ16 for C versus A & B, P< eβ16 for B versus A & C; MALAT1: P< eβ9 for C versus A & B; SOX11: P< eβ16 for B versus A & C, P< eβ9 for A versus B & C; GRIP2: P< eβ8 for B versus A & C). (d) Scatter plot showing the number of genes detected (β₯ 10 reads cutoff) versus the number of reads (n= 410 cells from combined single cell RNA-seq experiments after 2 weeks or 4 weeks of assembly in hSS-hCS). (e) Graph illustrating biologically variable transcripts (red circles) and non-variable transcripts (black circles) along with the technical noise from the ERCC spike in RNAs (blue dots). Green line shows the technical noise fit.
Immunocytochemistry and pharmacology in fused hSS-hCS(a, b, c, d) Representative images of immunostainings for SST, GAD67, GABA, CR, CB in Dlxi1/2b::eGFP+ cells after migration in fused hSS-hCS. (e) Scheme illustrating the pharmacological manipulation of Dlxi1/2b::eGFP+ cells that are migrating in hSS-hCS. (f, g, h, i) Quantification of Dlxi1/2b::eGFP+ cell migration before and after exposure to 100 nM of the CXCR4 antagonist AMD3100 (n= 8 cells from 2 hiPSC lines; paired t-tests, *P= 0.03 for number of saltations, **P= 0.006 for saltation length, **P= 0.006 for speed when mobile, *P= 0.02 for path directness). (j) Plot illustrating the trajectory of Dlxi1/2b::eGFP+ cells in fused hSS-hCS before and after exposure to AMD3100. Data are mean Β± s.e.m.
Migration of Dlx2i1/2b::eGFP cells in mouse and human forebrain brain slices versus hSS-hCS(a, b, c) Representative images of human fetal cortex at GW20 showing immunostaining with antibodies against GFAP, BCL11B (CTIP2) and GABA. (d) Representative image showing cell labeling with the Dlx2i1/2b::eGFP reporter in human forebrain at GW18 (6 days after lentivirus infection) (e, f) Representative immunostainings in cryosections of human tissue at GW18 showing co-localization of Dlx2i1/2b::eGFP with NKX2-1 and GABA. (g) Representative images showing cell labeling with the Dlx2i1/2b::eGFP reporter in hSS-hCS (9 days after assembly), in human forebrain (GW18) and in mouse slice cultures (E18). (h, i) Comparison of Dlx2i1/2b::eGFP+ cell size and quantification of the ratio of soma diameter to the length of the leading process in fused hSS-hCS (n= 25 cells from 4 hiPSC lines), human forebrain at GW18 (n= 19 cells; black) and GW20 (n= 15 cells; gray), hSS-derived cells cultured on E14 mouse forebrain slices (n= 14 cells), and E18 mouse forebrain slices (n= 30 cells from 2 litters) (one-way ANOVA, interaction F(3, 97)= 11.61, P= 0.001, Bonferroni post-hoc ***P< 0.001, **P< 0.05). (j, k, l) Comparison of the number of saltations (n= 56 cells from 2 hiPSC lines; one-way ANOVA, interaction F(2, 103)= 29.27, P= 0.001, Bonferroni post-hoc ***P< 0.001), saltation length (n= 44 cells from 3 hiPSC lines; one-way ANOVA, interaction F(2, 91)= 3.0, P= 0.50), speed when mobile (n= 38 cells from 3 hiPSC lines; one-way ANOVA, interaction F(2, 83)= 11.38, P= 0.001, Bonferroni post-hoc ***P< 0.001) for Dlx2i1/2b::eGFP+ in fused hSS-hCS, human fetal forebrain (GW18: n= 19 cells; GW20: n= 15 cells), and E18 mouse forebrain slices (n= 14 cells for saltation length and speed, n= 16 cells for number of saltations from 2 litters). Data are mean Β± s.e.m.
Derivation of TS hSS, migration and electroporation(a) Sequencing of PCR-amplified DNA showing the p.G406R mutation in exon 8a of CACNA1C in TS (subject: 8303). (b) Representative images of hiPSC colonies expressing pluripotency markers (OCT4, SSEA4) in one TS subject (c) Level of gene expression (RT-qPCR, normalized to GAPDH) for NKX2-1 showing no defects in ventral forebrain induction in TS (two-way ANOVA; interaction F(2,15)= 0.20, P= 0.81; TS versus Ctrl F(1,15)= 0.16, P= 0.68). (dβg) Representative immunostainings in cryosections of TS hSS (day 60) showing expression of NKX2-1, GABA, MAP2, GAD67, SST and CR. (h) Calcium imaging (Fura-2) in dissociated hCS derived from TS subjects and controls (Ctrl: n= 81 cells from 2 subjects; TS: n= 147 cells from 2 subjects). Quantification of residual intracellular calcium ([Ca2+]i) following 67 mM KCl depolarization of Ctrl and TS cells in hCS cells. Residual [Ca2+]i was calculated by dividing the plateau calcium (CβA) level by the peak calcium elevation (BβA); (t-test, ***P< 0.001). (i) Quantification of [Ca2+]i following depolarization of Ctrl and TS cells in hSS (t-test, ***P< 0.001). (j) Representative image of fused TS hSS-hCS showing Dlxi1/2b::eGFP expression and migration. (k, l) Quantification of the number of saltations and saltation length of Dlx2i1/2b::eGFP cells in fused hSS-hCS across multiple Ctrl and TS lines (related to Fig. 3d, e). (m) Quantification of the speed when mobile of Dlxi1/2b::eGFP cells in fused hSS-hCS (Ctrl: n= 21 cells from 3 hiPSC lines derived from 3 subjects; TS: n= 29 cells from 3 hiPSC lines derived from 3 subjects; TS-Ctrl hybrid: n= 12 cells from 3 hiPSC line shown combinations; one-way ANOVA with Dunnettβs multiple comparison test; ***P< 0.001). (n) Electroporation of cDNA encoding the TSβ and WTβ CaV1.2 channels into slices of mouse E14 ganglionic eminences (GE). (o) Representative example of time-lapse live imaging depicting the saltatory migration of GFP+ cells in slices electroporated with CAG::GFP and either the WTβor the TSβ CACNA1C. (p, q) Quantification of the number of saltations (t-test; **P< 0.01) and saltation length (t-test; ***P< 0.001) of GFP+ cells in electroporated mouse forebrain slices (WT: n= 33 cells; TS: n= 23 cells; from 3 litters). (r) Scheme illustrating pharmacological manipulation of LTCC during live imaging of fused hSS-hCS. (s) Quantification of speed when mobile following exposure to the LTCC blocker nimodipine (5 ΞΌM) (paired t-test; Ctrl: n= 13 cells from 3 hiPSC lines derived from 3 subjects, ***P< 0.001; TS: n= 12 cells from 2 hiPSC lines derived from 2 subjects, **P< 0.005). (t) Quantification of saltation length following exposure to roscovitine (15 ΞΌM) (paired t-test; Ctrl: n= 7 cells from 2 hiPSC lines derived from 2 subject, **P< 0.005; TS: n= 12 cells from 2 hiPSC lines derived from 2 subjects; ***P< 0.001). (u) Quantification of speed when mobile following exposure to roscovitine (15 ΞΌM) (paired t-tests; Ctrl: n= 9 cells from 2 hiPSC lines derived from 2 subjects, ***P< 0.001; TS: n= 12 cells from 2 hiPSC lines derived from 2 subjects; P= 0.05). Data are mean Β± s.e.m.
| # | Section | Preview |
|---|---|---|
| 60 | MATERIALS AND METHODS β Electrophysiology | Data were collected using a 1550A digitizer (Molecular Devices), a 700B patch-clamp amplifierβ¦ |
| 61 | MATERIALS AND METHODS β Statistics | Data are presented as mean Β± s.e.m. unless otherwise indicated. Distribution of the raw data wasβ¦ |
| Name | Type |
|---|---|
| 3D cultures | drug |
| AAV-DJ1 local | drug |
| accutase | drug |
| aCSF | drug |
| adaptor local | drug |
| agarose | drug |
| Agilent 2100 Bioanalyzer | drug |
| AlexaFluo Dyes local | drug |
| Allopregnanolone local | drug |
| AMD3100 local | drug |
| antiβCTIP2 local | drug |
| antiβGFAP local | drug |
| antiβOCT4 local | drug |
| antiβSSEA4 local | drug |
| antiβTBR1 local | drug |
| Applied Biosystems | drug |
| Aquamount local | drug |
| artificial cerebrospinal fluid | drug |
| astroglia | anatomy |
| autism spectrum disorder | phenotype |
| autism spectrum disorders | phenotype |
| Axoscop II microscope local | drug |
| B-27 supplement | drug |
| Basal Medium Eagle local | drug |
| Bdnf | gene |
| BD Resolve single cell whole transcriptome amplification workflow local | drug |
| brain circuits | anatomy |
| brain tissue | anatomy |
| BSA | drug |
| CaCl2 | drug |
| CACNA1C | gene |
| CAG-Cav1.2 plasmid local | drug |
| CAG::GFP plasmid local | drug |
| CALB1 | gene |
| CALB2 | gene |
| calcium | drug |
| calcium chloride | drug |
| Cav1.2-electroporated cells local | cohort |
| cDNA | drug |
| CELF4 | gene |
| cell culture membrane inserts local | drug |
| cell identification local | phenotype |
| cesium chloride local | drug |
| Chat | gene |
| chicken antiβGFP antibody local | drug |
| choroid plexus | anatomy |
| Clβ reversal local | phenotype |
| control | cohort |
| control cells local | cohort |
| control hiPSC cohort local | cohort |
| control subjects | cohort |
| cortex | anatomy |
| cortical neurons | anatomy |
| Costar membrane inserts local | drug |
| CTIP2 | gene |
| culture medium | drug |
| CXCR4 | gene |
| DCX | gene |
| dendritic branching complexity local | phenotype |
| D-(+)-Glucose local | drug |
| dibenzyl ether local | drug |
| dichloromethane local | drug |
| dispase | drug |
| Dlg4 | gene |
| Dlx1 | gene |
| DLX1/2B local | gene |
| DLX1/2B::eGFP+ cells local | phenotype |
| Dlx2 | gene |
| Dlx5 | gene |
| DLX6 | gene |
| Dlxi1/2b local | drug |
| Dlxi1/2b local | gene |
| Dlxi1/2b::eGFP local | drug |
| Dlxi1/2b::eGFP+ cells local | cohort |
| Dlxi1/2b::eGFP+ cells local | phenotype |
| Dlxi1/2b::eGFP lentivirus local | drug |
| Dlxi1/2b lentivirus local | drug |
| DMEM/F12 | drug |
| dNTP mix local | drug |
| dorsal forebrain | anatomy |
| dorsal progenitors local | phenotype |
| dorsomorphin | drug |
| double maximum action potential generation rate local | phenotype |
| E13β14 mouse slices local | anatomy |
| E14βE18 mouse embryos local | cohort |
| E17βE18 slices local | anatomy |
| EBSS local | drug |
| EDTA | drug |
| eEPSCs local | phenotype |
| EGF | drug |
| eGFP | drug |
| EGTA | drug |
| embryonic forebrain local | anatomy |
| embryonic stem cells local | drug |
| Emx1 | gene |
| epilepsy | phenotype |
| EPSCs | phenotype |
| ERBB4 | gene |
| ERCC local | drug |
| ethanol consumption | phenotype |
| excitatory postsynaptic current (EPSC) local | phenotype |
| FBS | drug |
| FEZF2 local | gene |
| FGF2 | drug |
| Fluo-4AM | drug |
| forebrain | anatomy |
| forebrain spheroids local | anatomy |
| Fos | gene |
| FOXG1 | gene |
| frontal cortex | anatomy |
| full sample | cohort |
| Fura-2AM local | drug |
| fused hSS-hCS local | cohort |
| GABA | phenotype |
| GABAA receptor | drug |
| GABAergic cells local | anatomy |
| GABAergic interneuron subdomain local | anatomy |
| gabazine local | drug |
| Gabazine local | drug |
| GAD1 | gene |
| GAD2 | gene |
| ganglionic eminence local | anatomy |
| GeneTex GTX13970 local | drug |
| GFAP | gene |
| GFP | drug |
| GLAST1 local | gene |
| glucose | drug |
| glutamatergic neurons | phenotype |
| Glutamax | drug |
| glutamine | drug |
| glycine | drug |
| Gphn | gene |
| GRIP2 local | gene |
| GSX2 local | gene |
| GTP | drug |
| GW18 local | cohort |
| GW20 local | cohort |
| Hanks local | drug |
| HBSS | drug |
| hCS local | anatomy |
| hCS | cohort |
| hCS-derived cells local | cohort |
| heparin | drug |
| HEPES | drug |
| HEPES buffer | drug |
| HES6 | gene |
| high-KCl Tyrodeβs solution local | drug |
| High Output sequencing kits local | drug |
| High-Sensitivity DNA chip local | drug |
| High Sensitivity DNA Chip | drug |
| Hoechst 33258 | drug |
| HOPX | gene |
| horse serum | drug |
| hPSC local | drug |
| hSS local | anatomy |
| hSS local | cohort |
| hSS-derived interneurons local | phenotype |
| hSS-hCS local | anatomy |
| hSS-IS local | cohort |
| hSS-ISA local | cohort |
| hSS-ISRA local | cohort |
| human brain | anatomy |
| human cells local | cohort |
| human cortical spheroids local | drug |
| human fetal Dlxi1/2b::eGFPβinfected cells local | cohort |
| human forebrain tissue local | anatomy |
| human subpallium spheroids local | drug |
| hydrogen peroxide | drug |
| IGF1 | gene |
| Illumina | drug |
| Illumina HiSeq 2500 instrument local | drug |
| ImageJ | drug |
| increased branching complexity local | phenotype |
| induced pluripotent stem cells | drug |
| inhibitory postsynaptic current (IPSC) local | phenotype |
| INSM1 local | gene |
| intermediate progenitors local | phenotype |
| interneuron | phenotype |
| interneuron migration | phenotype |
| interneuron motility local | phenotype |
| interneurons local | drug |
| intracellular calcium | phenotype |
| iPSCs | cohort |
| IS local | cohort |
| IWP-2 local | drug |
| KCl | drug |
| K-gluconate | drug |
| Knockout Serum local | drug |
| kynurenic acid local | drug |
| laminin | drug |
| Leica VT1200 vibratome local | drug |
| lentivirus | drug |
| Lenti-X concentrator local | drug |
| less efficient migration local | phenotype |
| LHX2 | gene |
| Life Technologies | drug |
| Lipofectamine 2000 | drug |
| low Clβ internal solution local | drug |
| LR White Resin local | drug |
| LTCC local | drug |
| L-type calcium channels local | drug |
| magnesium ATP local | drug |
| magnesium chloride | drug |
| MALAT1 local | gene |
| MAP2 | gene |
| mCherry | drug |
| medial ganglionic eminence | anatomy |
| methanol | drug |
| MgCl2 | drug |
| MgSO4 | drug |
| mice | cohort |
| migration | phenotype |
| migration defect local | phenotype |
| migration speed local | phenotype |
| mitochondrial gene local | gene |
| mouse Dlxi1/2b::eGFP+ cells local | cohort |
| mouse ganglionic eminences local | anatomy |
| mouse interneurons local | phenotype |
| mouse slices local | anatomy |
| Mycoplasma local | drug |
| N-2 local | drug |
| NaH2PO4 | drug |
| NaHCO3 | drug |
| Nernst equation local | drug |
| Neurobasal-A local | drug |
| neurodevelopmental disorder | phenotype |
| neurons | phenotype |
| neuropsychiatric disorders | phenotype |
| Nextera XT library prep kit local | drug |
| NextSeq 500 local | drug |
| nimodipine | drug |
| NKX2-1 | gene |
| NNAT | gene |
| non-essential amino acids | drug |
| normal goat serum | drug |
| NT3 | drug |
| NXPH1 | gene |
| OCT | drug |
| Oct4 | gene |
| olfactory interneurons local | phenotype |
| Olig2 | gene |
| oligodendrocyte progenitors local | anatomy |
| oligodendrocyte progenitors local | phenotype |
| Oligo-dT30VN local | drug |
| outer radial glia-like cells local | phenotype |
| pallium | anatomy |
| papain enzyme solution local | drug |
| paraformaldehyde | drug |
| path directness local | phenotype |
| patients | cohort |
| Pax6 | gene |
| PBX3 local | gene |
| pCAGIG plasmid local | drug |
| PCR | drug |
| penicillin | drug |
| personalized human microphysiological systems local | drug |
| PFA | drug |
| p.G406R local | variant |
| pG406R local | variant |
| phosphate-buffered saline | drug |
| physiological recordings local | phenotype |
| poly-l-ornithine | drug |
| poly-ornithine | drug |
| poly-ornithine/laminin local | drug |
| primary human fetal brain tissue local | anatomy |
| PTwH local | drug |
| Pvalb | gene |
| Qiagen | drug |
| Qiagen elution buffer local | drug |
| QuantStudio RT-PCR software local | drug |
| Qubit dsDNA HS Assay kit local | drug |
| Qubit High Sensitivity DNA Assay local | drug |
| RASD1 local | gene |
| Reln | gene |
| retinoic acid | drug |
| RNase-Free DNase set | drug |
| RNase inhibitor | drug |
| RNeasy Mini kit | drug |
| Roche local | drug |
| roscovitine | drug |
| SAG | drug |
| saltation frequency local | phenotype |
| saltation length local | phenotype |
| saltation speed local | phenotype |
| SB-431542 local | drug |
| SCG2 local | gene |
| secondary antibody | drug |
| sequencing libraries local | drug |
| sIPSCs | phenotype |
| SLC13A4 local | gene |
| Slc17a6 | gene |
| Slc17a7 | gene |
| SLC32A1 | gene |
| slicing local | phenotype |
| sodium phosphocreatine local | drug |
| Sox10 | gene |
| SOX11 | gene |
| SP8 | gene |
| specific neuronal cell types local | anatomy |
| speed when mobile local | phenotype |
| spontaneous calcium activity local | phenotype |
| SSEA4 local | gene |
| Sst | gene |
| Stanford Gene Vector and Virus Core local | cohort |
| STMN2 | gene |
| streptomycin | drug |
| striatal neurons local | phenotype |
| subdomains of the developing human brain local | anatomy |
| subpallium | anatomy |
| sucrose | drug |
| SuperScript III First-Strand Synthesis SuperMix local | drug |
| SYBR green | drug |
| SYN1 | gene |
| Tbr1 | gene |
| TBR2 | gene |
| TCF7L2 | gene |
| tetrahydrofuran local | drug |
| Th | gene |
| Timothy syndrome | phenotype |
| Tissue-Tek OCT Compound 4583 local | drug |
| Tourette syndrome | phenotype |
| Triton-X | drug |
| Triton X-100 | drug |
| TruSeq Rapid kit local | drug |
| Trypsin inhibitor | drug |
| TS | cohort |
| TS-Cav1.2 local | variant |
| TS-CaV1.2 local | variant |
| TS gain-of-function mutation local | variant |
| TS hiPSC cohort local | cohort |
| TS patients local | cohort |
| TTR local | gene |
| Tween-20 | drug |
| ventral forebrain local | anatomy |
| Ventral forebrain local | anatomy |
| ventral neural progenitors local | phenotype |
| ventricular zone | anatomy |
| VGAT | gene |
| vGLUT1 | gene |
| ViiA7 machine local | drug |
| VZ-like region local | anatomy |
| WT-Cav1.2 local | variant |
| Y-27632 local | drug |
| Ξ²-mercaptoethanol | drug |
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In this knowledge base
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Aberrant calcium signaling and neuronal activity in the L271H CACNA1D (Cav1.3) iPSC model of neurodevelopmental disease. | Tisch M et al. | β | 2026 | β |
| Advances and applications of brain organoids in central nervous system disorders: Bridging the gap from laboratory to clinic. | Fang C et al. | β | 2026 | β |
| Advances in cellular and structural engineering of brain organoids for disease modeling: A Comprehensive Review. | Kim H et al. | β | 2026 | β |
| Advances in the pathophysiological study of brain development: application of cerebral organoid combined with Spatial omics technology. | Wang J et al. | β | 2026 | β |
| Advances in three-dimensional modeling of ischemic injury. | Halkoluoto A et al. | β | 2026 | β |
| AI and organoid platforms for brain-targeted theranostics. | Ye R et al. | β | 2026 | β |
| Anesthetic-induced neurodevelopmental changes with region-specific responses to propofol in forebrain organoids. | She HQ et al. | β | 2026 | β |
| A novel iPSC model of Bryant-Li-Bhoj neurodevelopmental/neurodegenerative syndrome demonstrates the role of histone H3.3 in chromatin dynamics, neuronal differentiation, and maturation. | Sangree AK et al. | β | 2026 | β |
| Delayed forebrain excitatory and inhibitory neurogenesis in STRADA-related megalencephaly via mTOR hyperactivity. | Pan T et al. | β | 2026 | β |
| De novo H3.3K27M-altered diffuse midline glioma in human brainstem organoids to dissect GD2 CAR T cell function. | Bessler N et al. | β | 2026 | β |
| Dual developmental effects of ARX poly-alanine mutations on human cortical excitatory and inhibitory neurons. | Nieto-Estevez V et al. | β | 2026 | β |
| Generating Inhibitory Neuron Diversity through Morphogenic Patterning: From in vivo Studies to New in vitro Models. | Deutsch Guerrero T et al. | β | 2026 | β |
| Generation of spatially patterned human neural tube-like structures using microfluidic gradient devices. | Xue X et al. | β | 2026 | β |
| Human <i>in vitro</i> models of neurovasculature and the application to pre-clinical intracerebral haemorrhage research. | Crilly S et al. | β | 2026 | β |
| Human PSC-derived organoids model sympathetic ganglion development and its functional crosstalk with the heart. | Liu Y et al. | β | 2026 | β |
| Human stem cell-derived neurons establish functional inhibitory-excitatory cortical circuits in a chimeric transplantation model. | Hunt CPJ et al. | β | 2026 | β |
| In vitro models of cell competition: current approaches and future directions. | Baglamis S et al. | β | 2026 | β |
| Mechanistic Target of Rapamycin and Megalencephaly: Novel Research Strategies for Therapeutic Discovery. | Pan T et al. | β | 2026 | β |
| Microfluidic gradients create a stem cell model of the human central nervous system. | Serles P et al. | β | 2026 | β |
| Modelling adipose tissue-cancer crosstalk: a three-dimensional perspective. | Strusi G et al. | β | 2026 | β |
| Modelling brain tumours with organoids: towards precision medicine in neuro-oncology. | de Lucas Sanz M et al. | β | 2026 | β |
| Multi-omic analysis of guided and unguided forebrain organoids reveals differences in cellular composition and metabolic profiles. | ΓhlenschlΓ¦ger MS et al. | β | 2026 | β |
| Neuromechanobiology: Bridging Mechanobiology and Neuroscience Through Evidence and Open Questions. | Zimkowska K et al. | β | 2026 | β |
| Neuroplacentology of stress: Novel frontiers linking maternal mental health to offspring neurodevelopment. | Cruceanu C | β | 2026 | β |
| Now is not the time to defund human fetal tissue research. | β | β | 2026 | β |
| Parabiosis, Assembloids, Organoids (PAO). | Hong Y et al. | β | 2026 | β |
| Preconfigured neuronal firing sequences in human brain organoids. | van der Molen T et al. | β | 2026 | β |
| Proteomic profiling of brain organoids and extracellular vesicles identifies early Alzheimer's disease biomarkers and drug response heterogeneity. | Boyd RJ et al. | β | 2026 | β |
| Protocol for quality control screening of brain organoid morphology. | Chiaradia I et al. | β | 2026 | β |
| Reconstructing human corticogenesis: Insights from cerebral organoids into neurodevelopment and disease modeling. | Tenreiro MF et al. | β | 2026 | β |
| Self-organized anteroposterior regionalization of early midbrain and hindbrain/spinal cords using micropatterned human pluripotent stem cells. | Xie T et al. | β | 2026 | β |
| Stem cells in organogenesis and regeneration. | Mim TJ et al. | β | 2026 | β |
| Transcriptomic and phenotypic convergence of neurodevelopmental disorder risk genes in vitro and in vivo. | Fernandez Garcia M et al. | β | 2026 | β |
| Advances, challenges, and opportunities of human midbrain organoids for modelling of the dopaminergic system. | Fiorenzano A et al. | β | 2025 | β |
| Advances in Human Brain Organoids: Methodological Innovations and Future Directions for Drug Discovery. | Kanupriya K et al. | β | 2025 | β |
| Advances in lacrimal gland organoid development: Techniques and therapeutic applications. | Abdal Dayem A et al. | β | 2025 | β |
| Advances in Microfluidic Single-Cell RNA Sequencing and Spatial Transcriptomics. | Sun Y et al. | β | 2025 | β |
| Advancing autism research: Insights from brain organoid modeling. | Li CV et al. | β | 2025 | β |
| Advancing ex vivo functional whole-organ prostate gland model for regeneration and drug screening. | Subbiahanadar Chelladurai K et al. | β | 2025 | β |
| An Efficient Organoid Cutting Method for Long-Term Culture and High-Throughput Analyses. | Chartrain NA et al. | β | 2025 | β |
| An optimized method for directed differentiation of hypothalamic neural stem cells in a 3D culture system. | Luo J et al. | β | 2025 | β |
| APOE4 impacts cortical neurodevelopment and alters network formation in human brain organoids. | Meyer-Acosta KK et al. | β | 2025 | β |
| Application of brain organoids in neurodevelopmental disorders. | Zhao C et al. | β | 2025 | β |
| Beyond consciousness: Ethical, legal, and social issues in human brain organoid research and application. | Kataoka M et al. | β | 2025 | β |
| Beyond Structure: Next-Generation Electrophysiological Platforms for Functional Brain Organoids. | Cha JH et al. | β | 2025 | β |
| Bioelectronic Interfaces and Sensors for Neural Organoids. | Wang Q et al. | β | 2025 | β |
| Bioengineering innovations for neural organoids with enhanced fidelity and function. | Sun Y et al. | β | 2025 | β |
| Bioengineering tools for next-generation neural organoids. | O'Laughlin R et al. | β | 2025 | β |
| Bone organoid construction and evolution. | Hong Y et al. | β | 2025 | β |
| Brain Organoids and Assembloids-From Disease Modeling to Drug Discovery. | Ajongbolo AO et al. | β | 2025 | β |
| Brain organoids: building higher-order complexity and neural circuitry models. | Maisumu G et al. | β | 2025 | β |
| Brain Organoids: Tools for Understanding the Uniqueness and Individual Variability of the Human Brain. | Faravelli I et al. | β | 2025 | β |
| Brain Organoid Transplantation: A Comprehensive Guide to the Latest Advances and Practical Applications-A Systematic Review. | Shen YP et al. | β | 2025 | β |
| Brain tissues, assemble! Inside the push to build better brain models. | Dolgin E | β | 2025 | β |
| Breast cancer organoids: Advancements and applications in precision medicine. | Leung D et al. | β | 2025 | β |
| Cortical organoid-derived models of the melanoma brain metastatic niche enable prioritization of cancer-targeting drugs. | Krieg K et al. | β | 2025 | β |
| CRISPR-based genetically modified scaffold-free biomaterials for tissue engineering and regenerative medicine. | Chen Y et al. | β | 2025 | β |
| CRISPR screens in human neural organoids and assembloids. | Meng X et al. | β | 2025 | β |
| CXCR1 Depletion in Ly6C<sup>+</sup> cDC2 Alleviates Acute Lung Injury via Modulation of Th17/Treg Balance. | Li S et al. | β | 2025 | β |
| Deciphering the physiopathology of neurodevelopmental disorders using brain organoids. | Dionne O et al. | β | 2025 | β |
| Development of GABAergic Interneurons in the Human Cerebral Cortex. | MarΓn O | β | 2025 | β |
| Differentiation Defect Into GABAergic Neurons in Cerebral Organoids From Autism Patients. | Hali S et al. | β | 2025 | β |
| Disruptions in primary visual cortex physiology and function in a mouse model of Timothy syndrome. | Craddock R et al. | β | 2025 | β |
| Emerging brain organoids: 3D models to decipher, identify and revolutionize brain. | Zhao Y et al. | β | 2025 | β |
| Engineering brain organoids and organ-on-chip systems for modeling neurodevelopmental and neurodegenerative pathophysiology. | Banerjee S et al. | β | 2025 | β |
| Engineering the 3D structure of organoids. | Moss SP et al. | β | 2025 | β |
| Establishing dorsal-ventral patterning in human neural tube organoids with synthetic organizers. | Luo T et al. | β | 2025 | β |
| Establishment and transcriptomic characterization of canine organoids from multiple tissues. | Zdyrski C et al. | β | 2025 | β |
| Evolutionary divergence in CTCF-mediated chromatin topology drives transcriptional innovation in humans. | Wu X et al. | β | 2025 | β |
| Evolution of organoid genetics. | Klompstra TM et al. | β | 2025 | β |
| Examining the NEUROG2 lineage and associated gene expression in human cortical organoids. | Vasan L et al. | β | 2025 | β |
| Exploring human brain development and disease using assembloids. | Wu SR et al. | β | 2025 | β |
| Ex vivo functional whole organ in biomedical research: a review. | Subbiahanadar Chelladurai K et al. | β | 2025 | β |
| Fate plasticity of interneuron specification. | Mostajo-Radji MA et al. | β | 2025 | β |
| Forebrain assembloids support the development of fast-spiking human PVALB+ cortical interneurons and uncover schizophrenia-associated defects. | Walsh RM et al. | β | 2025 | β |
| From Cells to Organoids: Approaches, Regulatory Mechanisms, Applications, and Challenges of Organoids. | Wang L et al. | β | 2025 | β |
| From Organoids to Assembloids: Experimental Approaches to Study Human Neuropsychiatric Disorders. | Levy RJ et al. | β | 2025 | β |
| Functional Neurogenomics to Dissect Disease Mechanisms Across Models. | Zheng X et al. | β | 2025 | β |
| Generation, interrogation, and future applications of microglia-containing brain organoids. | Di Stefano J et al. | β | 2025 | β |
| Generation of Active Neurons from Mouse Embryonic Stem Cells Using Retinoic Acid and Purmorphamine. | Vajaria R et al. | β | 2025 | β |
| Generation of human nucleus basalis organoids with functional nbM-cortical cholinergic projections in transplanted assembloids. | Wang D et al. | β | 2025 | β |
| Generation of Neural Organoids and Their Application in Disease Modeling and Regenerative Medicine. | Huang R et al. | β | 2025 | β |
| Harnessing Intelligence from Brain Cells In Vitro. | Kagan BJ et al. | β | 2025 | β |
| Human assembloid model of the ascending neural sensory pathway. | Kim JI et al. | β | 2025 | β |
| Human brain organoids: an innovative model for neurological disorder research and therapy. | Li H et al. | β | 2025 | β |
| Human brain organoids for understanding substance use disorders. | Li K et al. | β | 2025 | β |
| Human neural organoid microphysiological systems show the building blocks necessary for basic learning and memory. | Alam El Din DM et al. | β | 2025 | β |
| Human stem cell-derived GABAergic interneuron development reveals early emergence of subtype diversity and gradual electrochemical maturation. | Bershteyn M et al. | β | 2025 | β |
| Immune and Immune-Integrated Organoids as NextGeneration Platforms for Disease Modeling. | Rashidan K et al. | β | 2025 | β |
| Inner ear organoids: Recent progress and potential applications. | Lou Y et al. | β | 2025 | β |
| Insulative Compression of Neuronal Tissues on Microelectrode Arrays by Perfluorodecalin Enhances Electrophysiological Measurements. | Duenki T et al. | β | 2025 | β |
| Interneuron migration defects during corticogenesis contribute to Dyrk1a haploinsufficiency syndrome pathogenesis. | Hinckelmann MV et al. | β | 2025 | β |
| iPSC-derived human cortical organoids display profound alterations of cellular homeostasis following SARS-CoV-2 infection and Spike protein exposure. | Cappelletti G et al. | β | 2025 | β |
| iPSC-derived neural organoids in dementia research: Recent advances and future directions. | Shima S et al. | β | 2025 | β |
| Liver organoids: Current advances and future applications for hepatology. | Kim Y et al. | β | 2025 | β |
| Long-term tracking of neural and oligodendroglial development in large-scale human cerebral organoids by noninvasive volumetric imaging. | Park S et al. | β | 2025 | β |
| <i>In vitro</i> technology and ADMET research in traditional Chinese medicine. | Xue J et al. | β | 2025 | β |
| Mapping human neurodevelopment-Brain organoids meet lineage tracing. | Liaci C et al. | β | 2025 | β |
| MEA-Based Graph Deviation Network for Early Autism Syndrome Signatures in Human Forebrain Organoids. | Mencattini A et al. | β | 2025 | β |
| MeCP2 regulates telencephalic development in human cerebral organoids. | Tenreiro MF et al. | β | 2025 | β |
| Merritt-Putnam Symposium | Developmental and Epileptic Encephalopathies-Current Concepts and Novel Approaches. | Scott RC et al. | β | 2025 | β |
| Microglia regulate GABAergic neurogenesis in prenatal human brain through IGF1. | Yu D et al. | β | 2025 | β |
| Micro-region transcriptomics profiling of cerebral organoids using a capillary-based microdissection system. | Ye K et al. | β | 2025 | β |
| Midline assembloids reveal regulators of human axon guidance. | Onesto MM et al. | β | 2025 | β |
| Mini-organs and early embryos in vitro: what is at stake? | Thetiot M et al. | β | 2025 | β |
| Modeling forebrain regional development and connectivity by human brain organoids. | Choe MS et al. | β | 2025 | β |
| Modelling human brain development and disease with organoids. | Birtele M et al. | β | 2025 | β |
| Modelling the human brain<i>in vitro</i>: biofabrication approaches for neural tissue engineering. | Borraccini A et al. | β | 2025 | β |
| Multi-organ model assessment of neurotoxicity following exposure of liver spheroids to drugs. | Wu W et al. | β | 2025 | β |
| Multiple sclerosis and infection: history, EBV, and the search for mechanism. | SoRelle ED et al. | β | 2025 | β |
| Multiplexing cortical brain organoids for the longitudinal dissection of developmental traits at single-cell resolution. | Caporale N et al. | β | 2025 | β |
| Muscle Organoid and Assembloid Systems. | Soydan HE et al. | β | 2025 | β |
| Neocortical neurogenesis: a proneural gene perspective. | Vasan L et al. | β | 2025 | β |
| Neurosteroid withdrawal disrupts GABAergic system development in human cortical organoids: implications for preterm birth. | Lacaille H et al. | β | 2025 | β |
| Next-Gen Stroke Models: The Promise of Assembloids and Organ-on-a-Chip Systems. | Lombardozzi G et al. | β | 2025 | β |
| Organoids in Genetic Disorders: from Disease Modeling to Translational Applications. | Zhu Y et al. | β | 2025 | β |
| Organoids - the future of pre-clinical development of AAV gene therapy for CNS disorders. | Kaiser VM et al. | β | 2025 | β |
| Peering into the mind: unraveling schizophrenia's secrets using models. | Nani JV et al. | β | 2025 | β |
| Personalized Human Astrocyte-Derived Region-Specific Forebrain Organoids Recapitulate Endogenous Pathological Features of Focal Cortical Dysplasia. | Xu J et al. | β | 2025 | β |
| Phenotypic complexities of rare heterozygous neurexin-1 deletions. | Fernando MB et al. | β | 2025 | β |
| Proof of concept for brain organoid-on-a-chip to create multiple domains in forebrain organoids. | Tsai YC et al. | β | 2025 | β |
| Protocol for generating human assembloids to investigate thalamocortical and corticothalamic synaptic transmission and plasticity. | Nityanandam A et al. | β | 2025 | β |
| Quantitative profiling of human brain organoid cell diversity across four protocols and multiple cell lines. | Naas J et al. | β | 2025 | β |
| Revolutionizing bladder cancer research: Harnessing 3D organoid technology to decode tumor heterogeneity and propel personalized therapeutics. | Kang H et al. | β | 2025 | β |
| SARS-CoV2 infection triggers inflammatory conditions and astrogliosis-related gene expression in long-term human cortical organoids. | Colinet M et al. | β | 2025 | β |
| Self-organization of sinusoidal vessels in pluripotent stem cell-derived human liver bud organoids. | Saiki N et al. | β | 2025 | β |
| Single-cell technology for cell-based drug delivery and pharmaceutical research. | Hu H et al. | β | 2025 | β |
| Single rosette-based generation of uniform cortical assembloids recapitulating cellular interactions between neurons and glial cells. | Kim E et al. | β | 2025 | β |
| Skeletal muscle, neuromuscular organoids and assembloids: a scoping review. | Yang JL et al. | β | 2025 | β |
| Thalamus-cortex interactions drive cell type-specific cortical development in human pluripotent stem cell-derived assembloids. | Nishimura M et al. | β | 2025 | β |
| The emergence of electrical activity in human brain organoids. | Mancinelli S et al. | β | 2025 | β |
| The Evolving Landscape of Functional Models of Autism Spectrum Disorder. | Ranjan J et al. | β | 2025 | β |
| The promise of cerebral organoids for neonatology. | Howard CE et al. | β | 2025 | β |
| The Specification and Functional Maturation of Sub-Cerebral Projection Neurons Derived from Human Induced Pluripotent Stem Cells. | Jordan Z et al. | β | 2025 | β |
| Towards advanced regenerative therapeutics to tackle cardio-cerebrovascular diseases. | Chen X et al. | β | 2025 | β |
| Toxicity assessment using neural organoids: innovative approaches and challenges. | Park SH et al. | β | 2025 | β |
| Tumor-adipose assembloids reveal cell-fate-transition-triggered multistage collective invasions. | Lei M et al. | β | 2025 | β |
| Understanding monocyte-driven neuroinflammation in Alzheimer's disease using human cortical organoid microphysiological systems. | Tian C et al. | β | 2025 | β |
| Variability vs. phenotype: Multimodal analysis of Dravet syndrome brain organoids powered by deep learning. | Turpin-Moreno I et al. | β | 2025 | β |
| 3D Multispheroid Assembly Strategies towards Tissue Engineering and Disease Modeling. | Zhu T et al. | β | 2024 | β |
| A 3D Bioprinted Cortical Organoid Platform for Modeling Human Brain Development. | Cadena MA et al. | β | 2024 | β |
| Advanced Cellular Models for Rare Disease Study: Exploring Neural, Muscle and Skeletal Organoids. | Bombieri C et al. | β | 2024 | β |
| Advances in human pluripotent stem cell reporter systems. | Puspita L et al. | β | 2024 | β |
| Advances in physiological and clinical relevance of hiPSC-derived brain models for precision medicine pipelines. | Imani Farahani N et al. | β | 2024 | β |
| A glia-enriched stem cell 3D model of the human brain mimics the glial-immune neurodegenerative phenotypes of multiple sclerosis. | Fagiani F et al. | β | 2024 | β |
| A molecular and cellular perspective on human brain evolution and tempo. | Lindhout FW et al. | β | 2024 | β |
| A Multi-Electrode Array Platform for Modeling Epilepsy Using Human Pluripotent Stem Cell-Derived Brain Assembloids. | Pan T et al. | β | 2024 | β |
| An integrated transcriptomic cell atlas of human neural organoids. | He Z et al. | β | 2024 | β |
| Antisense oligonucleotide therapeutic approach for Timothy syndrome. | Chen X et al. | β | 2024 | β |
| A patient-specific lung cancer assembloid model with heterogeneous tumor microenvironments. | Zhang Y et al. | β | 2024 | β |
| A patterned human neural tube model using microfluidic gradients. | Xue X et al. | β | 2024 | β |
| A polarized FGF8 source specifies frontotemporal signatures in spatially oriented cell populations of cortical assembloids. | Bosone C et al. | β | 2024 | β |
| Applications of multiphoton microscopy in imaging cerebral and retinal organoids. | Lacin ME et al. | β | 2024 | β |
| Assembloid models of cell-cell interaction to study tissue and disease biology. | Onesto MM et al. | β | 2024 | β |
| Basic models to advanced systems: harnessing the power of organoids-based microphysiological models of the human brain. | Boylin K et al. | β | 2024 | β |
| Bioengineering toolkits for potentiating organoid therapeutics. | Park S et al. | β | 2024 | β |
| Bioprinting of Cells, Organoids and Organs-on-a-Chip Together with Hydrogels Improves Structural and Mechanical Cues. | Mierke CT | β | 2024 | β |
| Brain organoid methodologies to explore mechanisms of disease in progressive multiple sclerosis. | SimΓ΅es-Abade MBC et al. | β | 2024 | β |
| Brain organoid protocols and limitations. | Zhao HH et al. | β | 2024 | β |
| Brain organoids: A new tool for modelling of neurodevelopmental disorders. | Aili Y et al. | β | 2024 | β |
| Brain organoids: A revolutionary tool for modeling neurological disorders and development of therapeutics. | Acharya P et al. | β | 2024 | β |
| Cell type specification and diversity in subpallial organoids. | Pavon N et al. | β | 2024 | β |
| Central nervous system vascularization in human embryos and neural organoids. | Boutom SM et al. | β | 2024 | β |
| Cerebral organoids display dynamic clonal growth and tunable tissue replenishment. | Lindenhofer D et al. | β | 2024 | β |
| Chronic Opioid Treatment Arrests Neurodevelopment and Alters Synaptic Activity in Human Midbrain Organoids. | Kim HS et al. | β | 2024 | β |
| Complex activity and short-term plasticity of human cerebral organoids reciprocally connected with axons. | Osaki T et al. | β | 2024 | β |
| Cortical brain organoid slices (cBOS) for the study of human neural cells in minimal networks. | Petersilie L et al. | β | 2024 | β |
| Cryopreservation of organoids: Strategies, innovation, and future prospects. | Han H et al. | β | 2024 | β |
| Deciphering potential vascularization factors of on-chip co-cultured hiPSC-derived cerebral organoids. | Shaji M et al. | β | 2024 | β |
| Decoding polygenic diseases: advances in noncoding variant prioritization and validation. | Chin IM et al. | β | 2024 | β |
| Design of neural organoids engineered by mechanical forces. | Suong DNA et al. | β | 2024 | β |
| Distinctive In Vitro Phenotypes in iPSC-Derived Neurons From Patients With Gain- and Loss-of-Function <i>SCN2A</i> Developmental and Epileptic Encephalopathy. | Mao M et al. | β | 2024 | β |
| Emergent trends in organ-on-a-chip applications for investigating metastasis within tumor microenvironment: A comprehensive bibliometric analysis. | He C et al. | β | 2024 | β |
| Engineering human midbrain organoid microphysiological systems to model prenatal PFOS exposure. | Tian C et al. | β | 2024 | β |
| Engineering immune organoids to regenerate host immune system. | Patel S et al. | β | 2024 | β |
| Engineering the Physical Microenvironment into Neural Organoids for Neurogenesis and Neurodevelopment. | Li M et al. | β | 2024 | β |
| Exploring the prospects, advancements, and challenges of <i>in vitro</i> modeling of the heart-brain axis. | Mabry SA et al. | β | 2024 | β |
| From wings to whiskers to stem cells: why every model matters in fragile X syndrome research. | Sandoval SO et al. | β | 2024 | β |
| Functional Neural Networks in Human Brain Organoids. | Gu L et al. | β | 2024 | β |
| Generating human neural diversity with a multiplexed morphogen screen in organoids. | Amin ND et al. | β | 2024 | β |
| Generation and characterization of cortical organoids from iPSC-derived dental pulp stem cells using traditional and innovative approaches. | Teles E Silva AL et al. | β | 2024 | β |
| Generation of human region-specific brain organoids with medullary spinal trigeminal nuclei. | Pang W et al. | β | 2024 | β |
| Generation of 'semi-guided' cortical organoids with complex neural oscillations. | Fitzgerald MQ et al. | β | 2024 | β |
| Genetics of human brain development. | Zhou Y et al. | β | 2024 | β |
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