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PI3Kβ and β-Catenin mediate EZH2 removal from promoters controlling human ESC stemness and primitive streak gene expression

ABSTRACT: PI3Kβ and β-Catenin mediate EZH2 removal from promoters controlling human ESC stemness and primitive streak gene expression

PROVIDER: PRJNA834818 | ENA |

REPOSITORIES: ENA

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PI3Kβ and β-Catenin mediate EZH2 removal from promoters controlling human ESC stemness and primitive streak gene expression

Project description:The mechanism governing the transition of human embryonic stem cells towards differentiated cells is only partially understood. To explore this transition, the activity and expression of the ubiquitous phosphoinositide-3-kinase (PI3K α and β) were modulated. This study reports a pathway that dismantles the repression imposed by the EZH2 polycomb repressor on an essential stemness gene, NODAL, and on transcription factors required at differentiation 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 an essential PI3Kβ-non-catalytic action for control of active-RAC1 levels, c-Jun-Nterminal-kinase activation and nuclear β-CATENIN accumulation. β-CATENIN deposition at promoters triggers the release of EZH2 repressor permitting both stemness maintenance (through control of NODAL) and correct differentiation, by allowing primitive streak master genes expression. PI3Kβ -mediated epigenetic control of EZH2/β-CATENIN might be modulated to direct stem cell differentiation.

2022-07-27 | GSE202163 | GEO

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

Project description: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.

| S-EPMC9561645 | biostudies-literature

Expression Profile of Chicken Primitive Streak (HH4) Tissues

2010-07-29 | GSE22230 | GEO

Induction of pluripotency in human somatic cells via a primitive streak-like state

Project description:During mammalian embryonic development, the primitive streak is initiates the differentiation of pluripotent epiblast cells into germ layers. Pluripotency can be reacquired in committed somatic cells using a combination of handful transcription factors, such as OCT3/4, SOX2, KLF4 and c-MYC (hereafter referred to as OSKM), albeit with low efficiency . Here we show that, during the OSKM-induced reprogramming process toward pluripotency in human cells, intermediate cells transiently show gene expression profiles resembling mesendoderm, which is a major component of the primitive streak. Based on these findings, we discover that forkhead box H1 (FOXH1), a transcription factor required for anterior primitive streak specification during early development, significantly enhances the reprogramming efficiency of human fibroblasts by promoting their maturation, including the mesenchymal to epithelial transition and the activation of late pluripotent markers. These results demonstrate that during the reprogramming process, human somatic cells go through a transient state that resembles mesendoderm. Human differentiated progeny derived from pluripotent stem cells, N=13 Human undifferentiated pluripotent stem cells, N=6 Transgenic ESC line, N=6 Human tissues, N=29 Human tissue-derived cells, N=20 Human nascent reprogrammed cells, N=95 Mouse cells, N=12

2014-04-24 | E-GEOD-50206 | biostudies-arrayexpress

Characterization of the self-organization of primitive streak and neuroectoderm fates

Project description:Characterization of the signaling requirements to determine primitive streak and neuroectoderm fates in mouse embryonic stem cells.

2022-01-20 | E-MTAB-10242 | biostudies-arrayexpress

Induction of pluripotency in human somatic cells via a primitive streak-like state

2014-04-24 | GSE50206 | GEO

Expression Profile of Chicken Primitive Streak (HH4) Tissues

Project description:In birds and mammals, all mesoderm cells are generated from the primitive streak. Nascent mesoderm cells contain unique dorso-ventral (D/V) identities depending on their relative ingression position along the streak. Molecular mechanisms controlling this initial phase of mesoderm diversification are not well-understood. Using chick model, we generated high-quality transcriptomic datasets of different streak regions and analyzed their molecular heterogeneity. Streak tissues were dissected from stage-matched HH4 chick embryos and were further divided into four equal pieces along its anterio-posterior length (termed “A”, “B”, “C” and “D”, with “A” representing most anterior and therefore most dorsal and “D” most posterior and therefore most ventral). Each of the four regions was represented by three independent samples (n=3), with each sample containing 5-7 μg total RNA derived from 85-93 pooled pieces. 5 μg of RNA from each sample were used to screen Affymetrix Chicken Genome Array without an amplification step.

2010-07-29 | E-GEOD-22230 | biostudies-arrayexpress

scRNA-Seq analysis of differentiation to primitive streak fate of mouse embryonic stem cells

Project description:scRNA-Seq analysis of differentiation to primitive streak fate of mouse embryonic stem cells

2022-01-20 | E-MTAB-10243 | biostudies-arrayexpress

Ventricular, Atrial and Outflow Tract heart progenitors arise from spatially and molecularly distinct regions of the primitive streak

Project description:Molecular characterisation of the primitive streak cells and cardiac progenitors

2021-03-16 | GSE153789 | GEO

scRNA-seq for mEpiSCs (epiblast stem cells) differentiated to posterior primitive streak (PPS) in vitro, in a monolayer

Project description:EpiSCs established from murine epiblast were differentiated to posterior primitive streak (PPS) and analyzed using scRNA-seq to investigate identity and homogeneity of the resulting population.

2022-11-30 | E-MTAB-12106 | biostudies-arrayexpress

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