Genetic Dissection of the Exit from Pluripotency in Mouse Embryonic Stem Cells by CRISPR-based Screening

The ground state naive pluripotency is established in the epiblast of the blastocyst and can be captured by culturing mouse embryonic stem cells (mESCs) with MEK and GSK3 inhibitors (2i). The transcription network that maintains pluripotency has been extensively studied with the indispensable core factors being Oct4, Sox2 and Nanog, together with other ancillary factors reinforcing the network. However, how this network is dissolved at the onset of differentiation is still not fully understood. To identify genes required for differentiation in an unbiased fashion, a genome-wide CRISPR-Cas9-mediated screen in Rex1GFPd2 mESCs was conducted.