The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 5290002, Israel.
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 5290002, Israel.
Stem Cell Reports. 2020 Nov 10;15(5):1037-1046. doi: 10.1016/j.stemcr.2020.10.002. Epub 2020 Oct 29.
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.
SWI/SNF 复合物的表观遗传调控对于人多能干细胞（hPSC）的正常自我更新能力和多能性至关重要。已经表明，该复合物的不同亚基在这种调控中具有独特的作用。具体而言，SMARCB1 亚基已被证明可调节不同类型细胞（包括 hPSC）中增强子的活性。在这里，我们报告了条件性 hPSC 系的建立，使 SMARCB1 表达从完全功能丧失到显著过表达得到控制。使用该系统，我们表明，任何偏离正常 SMARCB1 表达的情况都会导致细胞分化。我们进一步发现，SMARCB1 表达对于 hPSC 分化为祖细胞不是必需的，而是对于分化的后期阶段是必需的。最后，我们确定 SMARCB1 是 hPSC 中细胞-细胞和细胞-ECM 相互作用调节的关键因素，并表明这种调节至少部分是由 WNT 途径介导的。
