MLL1 Inhibition and Vitamin D Signaling Cooperate to Facilitate the Expanded Pluripotency State

• DOI: 10.1016/j.celrep.2019.10.074
• Publication Date: 2019-11-26T22:10:17Z
• Authors: Hui Zhang; Le Tran Phuc Khoa; Fengbiao Mao; Hanshi Xu; Bo Zhou; Yu Han; Monique O’Leary; Asma Nusrat; Li Wang; Thomas L. Saunders; Yali Dou
• Keywords: Cell fate determination; Histone Methylation; Totipotent

Dynamic establishment of histone modifications in early development coincides with programed cell fate restriction and loss totipotency beyond the blastocyst stage. Causal function histone-modifying enzymes this process remains to be defined. Here we show that inhibiting methyltransferase MLL1 reprograms naive embryonic stem cells (ESCs) expanded pluripotent (EPSCs), differentiation potential toward both extraembryonic lineages vitro vivo. inhibition or deletion upregulates gene signatures blastomere development. The restricting induction EPSCs is mediated partly by Gc, which regulates cellular response vitamin D signaling. Combined treatment inhibitor 1α,25-dihydroxyvitamin D3 (1,25-(OH)2D3) cooperatively enhanced functionality EPSCs, triggering an extended 2C-like state robust totipotent-like property Our study sheds light on interplay between epigenetics pathway determination.