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 复合体的表观遗传调控对于人类多能干细胞 (hPSC) 的正常自我更新能力和多能性至关重要。已经表明复合体的不同亚基在该调节中具有不同的作用。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 hPSC 系的建立，从而能够控制 SMARCB1 表达从完全丧失功能到显着过度表达。使用该系统，我们表明与正常 SMARCB1 表达的任何偏差都会导致细胞分化。我们进一步发现 SMARCB1 表达不是 hPSC 分化为祖细胞所必需的，而是分化的后期阶段所必需的。最后，