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Chunk #42 — Discusion

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Fusion of Regionally Specified hPSC-Derived Organoids Models Human Brain Development and Interneuron Migration.
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In parallel with our studies, two groups recently reported methods generating fused ventral and dorsal forebrain organoids as a model of interneuron migration (Bagley et al., 2017; Birey et al., 2017). In all three studies, patterning factors for SHH signaling (e.g. SHH and purmorphamine in our current study, and smoothened agonist SAG in Birey et al. and Bagley et al.) were used to induce ventral fate. The detailed protocols for organoid generation and fusion, however, differ from one another. For instance, Birey et al. begin with intact hPSC colonies rather than single cells to form the organoids (Birey et al., 2017). On the other hand, Bagley et al. generate organoids from the single cells dissociated from hPSC colonies like our approach (Bagley et al., 2017). While dual SMAD inhibitors by Birey et al. and additional Wnt inhibitor by us are used to induce neuroectoderm from hPSCs, Bagley et al. do not include specific neural induction factors. In forming fused organoids, Bagley et al. used a single Matrigel droplet to embed two organoids (Bagley et al., 2017), while the static fusion