Human Pluripotent Stem Cell Fate Regulation by SMARCB1
| Autor: | Achia Urbach, Hiba Waldman Ben-Asher, Orly Yaron, Ilana Carmel-Gross, Etgar Levy, Leah Armon |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
extra cellular matrix Cellular differentiation Human Embryonic Stem Cells Induced Pluripotent Stem Cells SMARCB1 Cell Communication Biology Biochemistry Cell Line Epigenesis Genetic Extracellular matrix 03 medical and health sciences 0302 clinical medicine Report Genetics Humans pluripotent stem cell Epigenetics Progenitor cell Induced pluripotent stem cell Enhancer Wnt Signaling Pathway Loss function Stem Cells Wnt signaling pathway Cell Differentiation Cell Biology SMARCB1 Protein Cell biology Extracellular Matrix 030104 developmental biology Gene Expression Regulation 030217 neurology & neurosurgery Developmental Biology SWI/SNF complex |
| Zdroj: | Stem Cell Reports |
| ISSN: | 2213-6711 |
| Popis: | Summary 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. Highlights • SMARCB1 levels have to be precisely regulated in hPSCs • SMARCB1 loss of function affects hPSC self-renewal capacity and pluripotency • SMARCB1 overexpression leads to hPSC differentiation • SMARCB1 is required for normal cell-cell and cell-ECM interactions in hPSCs Using conditional loss of function and overexpression systems, Urbach and colleagues show that any deviation from SMARCB1 normal expression levels affects the self-renewal capacity of the hPSCs. They further show that SMARCB1 is required to maintain the differentiation capacity of the cells. Finally, they demonstrate the critical role of SMARCB1 in cell-cell and cell-ECM interactions in hPSCs. |
| Databáze: | OpenAIRE |
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