University of Nottingham

Masaki Kinoshita

Formative state of pluripotency was recently proposed and formative stem (FS) cells were established from mouse and human embryos. It has unique features of pluripotency in early post-implantation embryos such as blastocyst chimaera competency and direct germ cell differentiation potency. In formative phase, earlier naïve blastocyst cells become competent to respond to differentiation signals, which embryos can initiate the gastrulation. In other words, the genes essential for this state play important roles for embryos to gastrulate. In humans, about 30% of miscarriage occurs at this stage, so elucidating gene regulatory networks helps understanding of such early pregnancy loss. We previously identified Oct4 and Otx2 as essential genes for formative state maintenance; however, the entire gene regulatory network is still largely unknown. We performed genome-wide CRISPR/Cas9 based screening and identified essential genes for the mouse formative pluripotency maintenance. We will validate the screening results and elucidate individual gene functions required for the formative pluripotency using omics approach.