报告题目：From genetic association to disease biology: human induced pluripotent stem cell (iPSC) as a cellular model for schizophrenia
报 告 人：段聚宝教授
Director, Unit of Functional Genomics in Psychiatry
Center for Psychiatric Genetics
North Shore University Health System, Evanston, IL
Assistant Professor, University of Chicago
摘要：Schizophrenia is a devastating mental disorder afflicting 1% of the population. Recent genome-wide association studies (GWAS) of schizophrenia have identified >100 risk loci. However, the causal variants/genes remain largely unknown, which hinders the translation of GWAS findings into disease biology and drug targets. Most disease risk variants lie within noncoding parts of the genome that are poorly annotated, and their functional interpretation has been challenging. This presentation provides a functional genomics framework of bridging the recent genetic findings to disease biology using human neurons differentiated from induced pluripotent stem cells (iPSCs) as a cellular model. In specific, we performed a genome-wide profiling of open chromatin regions during iPSC differentiation into glutamatergic neurons, and showed that CRISPR/Cas9 editing of open chromatin sequence and flanking schizophrenia risk variant at one of the strongest schizophrenia risk loci impacts adjacent gene expression and neurodevelopment in human iPSC-derived neurons.