Using human stem cell derived in vitro modeling to characterize the effect of MYCN overexpression on early hSAP development and tumor formation
In this study we use human stem cell derived in vitro modelling to characterize the effect of MYCN overexpression on early hSAP development and tumor formation. We developed and characterized a human in vitro pluripotent stem cell-based model via sequential single-cell RNA sequencing throughout sympathoadrenal development. Overall design: We differentiated an induced pluripotent stem cell (iPSC) line with a doxycycline inducible MYCN construct along the hSAP developmental trajectory in vitro. We induced MYCN overexpression at multiple timepoints during the critical time frame for the hSAP developmental window during differentiation, as defined by expression changes of key genes including PLP1, ASCL1 and STMN2, covering both early and late hSAP development. During this window we induced MYCN overexpression for 48hrs at four time-points (day 24, 26, 28 and 30). We then collected cells for single cell RNA-seq.