अमूर्त
Understanding human neural crest: from enteric nervous system development to Hirschsprung Disease, using single-cell transcriptomics analysis and pluripotent stem cell (PSC)-based models
Elly NganThe neural crest (NC) is a transient population of multipotent progenitor cells in vertebrates, contributing to the formation of various organ systems. Aberrant NC development results in a myriad of birth defects and diseases, such as Hirschsprung (HSCR) disease which is attributed to the developmental defects of enteric NC. Directed differentiation protocols for derivation of NC from human pluripotent stem cells (hPSCs) have been established by various research groups and used for disease modeling and regenerative medicine. Recently, we applied single-cell RNA sequencing (scRNA-Seq) to reveal the molecular dynamics underlying the neuronal lineage differentiation trajectory of human PSC-derived enteric NCs. We demonstrated that the in vitro differentiation of human enteric NCs closely resembles the development of mouse enteric NCs in vivo and defined the transcriptional circuits mediating the cellular differentiation. Using a similar approach, we reconstructed the pathogenesis of HSCR and further defined the core regulome underlying the disease pathogenesis. In my talk, I will highlight our latest findings on using hPSC stem cell models to reveal the molecular control of various cellular processes during the development of human NC and HSCR pathogenesin.