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Chunk #3 — Introduction

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Analysis of induced pluripotent stem cells carrying 22q11.2 deletion.
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To gain a deeper understanding of the changes leading to schizophrenia during neurodevelopment,14 cellular models are needed to help identify biological mechanisms that are perturbed during this process. Such cellular models are now possible because of the availability of human-induced pluripotent stem cells (hiPSCs) derived from schizophrenia patients and their differentiated neural stem or progenitor cells and neurons.15, 16, 17, 18, 19 Using such a model, we initially examined cell morphologies and differentiation efficiencies of hiPSCs to neurospheres (mainly consisting of neural stem/progenitor cells) and further to neuronal cells. Neurospheres derived from hiPSCs from subjects with schizophrenia showed abnormal phenotypes similar to neurospheres derived from Dgcr8 heterozygous knockout mice.10 Therefore, we focused on the changes in microRNA (miRNA) expression potentially elicited by DGCR8 haploinsufficiency, and investigated subsequent molecular cascades.