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Zhexing Wen

Department of Psychiatry and Behavioral Sciences at Emory University

Dr. Zhexing Wen received his PhD training at the Rutgers University in 2008. In 2009, he joined Drs. Hongjun Song and Guo-li Ming’s laboratories at Johns Hopkins University as a postdoctoral fellow. In 2016, Dr. Wen joined the Department of Psychiatry and Behavioral Sciences at Emory University as an Assistant Professor. The research of Dr. Wen’s laboratory centers on understanding the molecular mechanisms underlying neuropsychiatric disorders. In particular, he is interested in using patient-derived induced-pluripotent stem cells (iPSCs) to elucidate the biological functions of causal/risk genetic and environmental factors in neuropsychiatric disorders, identify pathological developmental processes that may contribute to the etiology of these complex diseases, and translate such knowledge into therapeutic targets for developing novel treatments.

Molecular dynamics associated with development of human GABAergic interneurons

Abstract:

GABAergic interneurons (GINs) are a heterogeneous population of inhibitory neurons that collectively contribute to the maintenance of normal neuronal excitability and network activity. Several homeobox and basic helix-loop-helix transcription factors are known to contribute to neural patterning and early GIN fate specification, including DLX1/DLX2, NKX2.1, ASCL1, and MASH1. However, much less is known about the networks of transcription factors and genetic elements that contribute to mature GIN function. In particular, there is a knowledge gap in the epigenomic dynamics of developing GINs, which may direct interneuron-specific expression patterns. Identification of these regulatory components may provide new insight into the pathways underlying proper GIN activity, while also denoting potential therapeutic targets for GIN-associated disorders, such as schizophrenia and epilepsy. Here, we differentiated human induced pluripotent stem cells (iPSCs) derived from two healthy male controls into GINs with 81-85% efficiency. To examine temporal changes in gene expression and chromatin accessibility, cells were collected at three time points for RNA-seq and ATAC-seq analysis: neural progenitor cells (NPCs) at 22 days post-differentiation (D22), then GINs at D50 and D78. By comparing differentially accessible regions (DARs) of chromatin that were shared between the two iPSC lines, we identified 13,221 genomic regions that correlated with temporal changes in gene expression unique to mature GINs. We also classified several transcription factors (TFs) that were increasingly enriched at DARs during differentiation, indicating regulatory networks that may underlie GIN function. Furthermore, we identified several genes that may be especially relevant to mature GIN function in schizophrenia patients. Collectively, these data represent a comprehensive analysis of transcriptomic and epigenomic changes that occur during GIN development.