Ye Ying, Chen Xi, Zhang Wensheng
Cam-Su Genomic Resource Center, Medical College of Soochow University, Suzhou, China.
Department of Biology, Southern University of Science and Technology, Shenzhen, China.
Front Cell Dev Biol. 2021 Jan 18;8:626383. doi: 10.3389/fcell.2020.626383. eCollection 2020.
The unique capability of embryonic stem cells (ESCs) to maintain and adjust the equilibrium between self-renewal and multi-lineage cellular differentiation contributes indispensably to the integrity of all developmental processes, leading to the advent of an organism in its adult form. The ESC fate decision to favor self-renewal or differentiation into specific cellular lineages largely depends on transcriptome modulations through gene expression regulations. Chromatin remodeling complexes play instrumental roles to promote chromatin structural changes resulting in gene expression changes that are key to the ESC fate choices governing the equilibrium between pluripotency and differentiation. BAF (Brg/Brahma-associated factors) or mammalian SWI/SNF complexes employ energy generated by ATP hydrolysis to change chromatin states, thereby governing the accessibility of transcriptional regulators that ultimately affect transcriptome and cell fate. Interestingly, the requirement of BAF complex in self-renewal and differentiation of ESCs has been recently shown by genetic studies through gene expression modulations of various BAF components in ESCs, although the precise molecular mechanisms by which BAF complex influences ESC fate choice remain largely underexplored. This review surveys these recent progresses of BAF complex on ESC functions, with a focus on its role of conditioning the pluripotency and differentiation balance of ESCs. A discussion of the mechanistic bases underlying the genetic requirements for BAF in ESC biology as well as the outcomes of its interplays with key transcription factors or other chromatin remodelers in ESCs will be highlighted.
胚胎干细胞(ESC)维持并调节自我更新与多谱系细胞分化之间平衡的独特能力,对所有发育过程的完整性不可或缺,最终促成生物体发育为成熟个体。ESC倾向于自我更新还是分化为特定细胞谱系的命运决定,很大程度上取决于通过基因表达调控实现的转录组调节。染色质重塑复合物在促进染色质结构变化从而导致基因表达改变方面发挥着重要作用,而这些基因表达变化是ESC命运选择的关键,决定着多能性与分化之间的平衡。BAF(Brg/Brahma相关因子)或哺乳动物SWI/SNF复合物利用ATP水解产生的能量来改变染色质状态,从而控制转录调节因子的可及性,最终影响转录组和细胞命运。有趣的是,最近通过对ESC中各种BAF成分进行基因表达调控的遗传学研究表明了BAF复合物在ESC自我更新和分化中的必要性,尽管BAF复合物影响ESC命运选择的确切分子机制仍未得到充分探索。本综述概述了BAF复合物在ESC功能方面的这些最新进展,重点关注其在调节ESC多能性和分化平衡方面的作用。将着重讨论BAF在ESC生物学中的遗传学需求的机制基础,以及它与ESC中的关键转录因子或其他染色质重塑因子相互作用的结果。