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Human Pluripotent Stem Cell Fate Regulation by SMARCB1.

ABSTRACT: Epigenetic regulation by the SWI/SNF complex is essential for normal self-renewal capacity and pluripotency of human pluripotent stem cells (hPSCs). It has been shown that different subunits of the complex have a distinct role in this regulation. Specifically, the SMARCB1 subunit has been shown to regulate the activity of enhancers in diverse types of cells, including hPSCs. Here, we report the establishment of conditional hPSC lines, enabling control of SMARCB1 expression from complete loss of function to significant overexpression. Using this system, we show that any deviation from normal SMARCB1 expression leads to cell differentiation. We further found that SMARCB1 expression is not required for differentiation of hPSCs into progenitor cells, but rather for later stages of differentiation. Finally, we identify SMARCB1 as a critical player in regulation of cell-cell and cell-ECM interactions in hPSCs and show that this regulation is mediated at least in part by the WNT pathway.

SUBMITTER: Carmel-Gross I

PROVIDER: S-EPMC7664050 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Human Pluripotent Stem Cell Fate Regulation by SMARCB1.

Carmel-Gross Ilana I Levy Etgar E Armon Leah L Yaron Orly O Waldman Ben-Asher Hiba H Urbach Achia A

Stem cell reports 20201029 5

Epigenetic regulation by the SWI/SNF complex is essential for normal self-renewal capacity and pluripotency of human pluripotent stem cells (hPSCs). It has been shown that different subunits of the complex have a distinct role in this regulation. Specifically, the SMARCB1 subunit has been shown to regulate the activity of enhancers in diverse types of cells, including hPSCs. Here, we report the establishment of conditional hPSC lines, enabling control of SMARCB1 expression from complete loss of ...[more]

PMID: 33125876

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Human pluripotent stem cell fate regulation by SMARCB1

Project description:Epigenetic regulation by the SWI/SNF complex is essential for normal self-renewal capacity and pluripotency of human pluripotent stem cells (hPSCs). It has been shown that different subunits of the complex have a distinct role in this regulation. Specifically, the SMARCB1 core subunit has been shown to regulate the activity of enhancers in diverse types of cells, including hPSCs. Here we report the establishment of conditional hPSC lines, which enable the control of SMARCB1 expression from complete loss of function (LOF) to significant overexpression. Using this system, we show that any deviation from normal SMARCB1 expression leads to rapid differentiation of the cells. We further found that SMARCB1 expression is not required for the differentiation of hPSCs into progenitor cells of the three germ layers, but rather for later stages of differentiation. Moreover, we identify SMARCB1 as a critical player in the regulation of cell-cell and cell-extracellular matrix (ECM) interactions in hPSCs. Finally, our results show that complete SMARCB1 LOF affects hPSC fate in a different way than the effect of partial downregulation of the gene and thus emphasizes the complex regulation of hPSCs by SMARCB1.

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