PI3Kβ-regulated β-catenin mediates EZH2 removal from promoters controlling primed human ESC stemness and primitive streak gene expression.

Autor:	Yadav S; Department of Immunology and Oncology, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain., Garrido A; Department of Immunology and Oncology, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain., Hernández MC; Department of Immunology and Oncology, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain., Oliveros JC; Department of Systems Biology, Bioinformatics, Centro Nacional de Biotecnología/CSIC, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain., Pérez-García V; Centro de Investigación Príncipe Felipe, Eduardo Primo Yúfera, 46013 Valencia, Spain., Fraga MF; Nanomaterials and Nanotechnology Research Center/CSIC, Health Research Institute of Asturias (ISPA), Institute of Oncology of Asturias (IUOPA), Research Center for Rare Diseases (CIBERER), 33011 Oviedo, Asturias, Spain., Carrera AC; Department of Immunology and Oncology, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain. Electronic address: acarrera@cnb.csic.es.
Jazyk:	angličtina
Zdroj:	Stem cell reports [Stem Cell Reports] 2022 Oct 11; Vol. 17 (10), pp. 2239-2255. Date of Electronic Publication: 2022 Sep 29.
DOI:	10.1016/j.stemcr.2022.09.003
Abstrakt:	The mechanism governing the transition of human embryonic stem cells (hESCs) toward differentiated cells is only partially understood. To explore this transition, the activity and expression of the ubiquitous phosphatidylinositol 3-kinase (PI3Kα and PI3Kβ) were modulated in primed hESCs. The study reports a pathway that dismantles the restraint imposed by the EZH2 polycomb repressor on an essential stemness gene, NODAL, and on transcription factors required to trigger primitive streak formation. The primitive streak is the site where gastrulation begins to give rise to the three embryonic cell layers from which all human tissues derive. The pathway involves a PI3Kβ non-catalytic action that controls nuclear/active RAC1 levels, activation of JNK (Jun N-terminal kinase) and nuclear β-catenin accumulation. β-Catenin deposition at promoters triggers release of the EZH2 repressor, permitting stemness maintenance (through control of NODAL) and correct differentiation by allowing primitive streak master gene expression. PI3Kβ epigenetic control of EZH2/β-catenin might be modulated to direct stem cell differentiation. Competing Interests: Conflict of interests The authors declare no competing interests. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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