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Right here, by doing a CRISPR-based loss-of-function display in embryonic stem cells (ESCs), we identify PcG gene Mga active in the repression of endodermal transcription element Gata6 We report that deletion of Mga results in peri-implantation embryonic lethality in mice. We further demonstrate that Mga-null ESCs exhibit impaired self-renewal and spontaneous differentiation to primitive endoderm (PE). Our data help a model in which Mga might serve as a scaffold for PRC1.6 assembly and guide this