Embryonic stem cells (ESCs) maintain their cellular identity through the systematic regulation of master transcription factors and chromatin remodeling complexes. Recent work has shown that the unusually large-scale enhancers—namely super-enhancers (SEs), on which BRD4, a member of the bromodomain and extraterminal domain (BET) family is highly enriched—could regulate pluripotency-related transcription factors. Moreover, inhibition of BRD4 binding on SEs has been shown to induce the differentiation of ESCs. However, the underlying mechanism of BRD4 inhibition-mediated stem cell differentiation remains elusive. Here we show that both mouse and human ESCs lose their capacity for self-renewal upon treatment with JQ1, a selective inhibitor of BET family including BRD4, with rapid suppression of pluripotency-associated genes. Notably, a high concentration of JQ1 could selectively eliminate ESCs via apoptosis, without affecting the functionality of differentiated somatic cells from ESCs, suggesting that inhibition of BET may have a beneficial effect on the development of pluripotent stem cell-based cell therapy.

胚胎干细胞 (ESC) 通过主转录因子和染色质重塑复合物的系统调节来维持其细胞特性。最近的研究表明，异常大规模的增强子——即超级增强子 (SEs)，溴结构域和末端外结构域 (BET) 家族的成员 BRD4 在其上高度富集——可以调节多能性相关转录因子。此外，已证明抑制 BRD4 与 SE 的结合可诱导 ESC 的分化。然而，BRD4 抑制介导的干细胞分化的潜在机制仍然难以捉摸。在这里，我们表明小鼠和人类 ESC 在用 JQ1 处理后都失去了自我更新的能力，JQ1 是 BET 家族（包括 BRD4）的选择性抑制剂，可快速抑制多能性相关基因。尤其，