Pluto Biosciences, Inc

GSE145653: Cooperative genetic networks drive a mammalian cell state transition

Bulk RNA sequencing

In the mammalian embryo epiblast cells must exit their nave state and differentiate to acquire formative pluripotency. This cell-state-transition is recapitulated in mouse embryonic stem cells (ESCs), which undergo pluripotency-progression in defined conditions in vitro. Here we combined genetic screens in haploid ESCs with CRISPR/Cas9 gene-disruption, large-scale transcriptomics and computational systems-biology to delineate the regulatory circuits governing nave-state-exit. Transcriptome profiles for 73 knockouts mostly align on the in vivo trajectory from naive to formative epiblast. We identified 496 nave-associated genes tightly connected to the epiblast state and largely conserved primate embryos. Systematic analysis of mutant transcriptomes highlighted discrete regulatory clusters, which are under control of one or more of five signaling pathways. Thus, a pivotal mammalian cell state transition is driven by multiple genes whose actions are funneled through a handful of complementary circuits in vitro and in vivo. SOURCE: Andreas Beyer (, - Systems Biology University of Cologne

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