Peking University School of Basic Medical Sciences, China (People's Republic)
Abstract: The initiation of major zygotic genome activation (ZGA) is crucial for human early embryogenesis. However, the gene regulation network (GRN) behind major ZGA in humans remain largely unknown. Transcription factors (TFs) are master regulators of GRN. To better understand the mechanism behind ZGA, we performed a CRISPR-based activation screen of all the human TFs in human extended pluripotent stem cells (hEPSCs) and identified unreported candidates as major ZGA regulators. Further evaluation of these candidates revealed that over-expression of several targets activated totipotent features that differ from known totipotency and ZGA regulators in hEPSCs. Importantly, knockdown of key candidates arrested human embryo development prior to the 8-cell embryo stage, indicating an unreported mechanism of TFs mediating totipotency in vitro, accompanied by the suppression of a set of 4-cell embryo enriched genes. Our study provided valuable resources for the investigation of totipotency and major ZGA regulation, and brought up new model for TFs regulating ZGA.
Funding Source: The National Key R&D Program of China (2021YFA1100300), the National Natural Science Foundation of China (32288102), the Beijing Natural Science Foundation (JQ24042), the National Natural Science Foundation of China (32370843).
