Zheng Zi Hao, Sam Tsz Wing, Zeng YingYing, Chu Justin Jang Hann, Loh Yuin-Han
Laboratory for Epigenetics, Stem Cells & Cell Therapy, Programme in Stem Cell, Regenerative Medicine and Aging, ASTAR Institute of Molecular and Cell Biology, Singapore 138673.
Department of Physiology, NUS Yong Loo Lin School of Medicine, 2 Medical Drive, MD9, Singapore 117593.
Stem Cells Int. 2021 Feb 2;2021:8817581. doi: 10.1155/2021/8817581. eCollection 2021.
The regulation of mammalian stem cell fate during differentiation is complex and can be delineated across many levels. At the chromatin level, the replacement of histone variants by chromatin-modifying proteins, enrichment of specific active and repressive histone modifications, long-range gene interactions, and topological changes all play crucial roles in the determination of cell fate. These processes control regulatory elements of critical transcriptional factors, thereby establishing the networks unique to different cell fates and initiate waves of distinctive transcription events. Due to the technical challenges posed by previous methods, it was difficult to decipher the mechanism of cell fate determination at early embryogenesis through chromatin regulation. Recently, single-cell approaches have revolutionised the field of developmental biology, allowing unprecedented insights into chromatin structure and interactions in early lineage segregation events during differentiation. Here, we review the recent technological advancements and how they have furthered our understanding of chromatin regulation during early differentiation events.
哺乳动物干细胞在分化过程中的命运调控是复杂的,且可以在多个层面进行描述。在染色质水平,染色质修饰蛋白对组蛋白变体的替换、特定活性和抑制性组蛋白修饰的富集、长程基因相互作用以及拓扑变化,在细胞命运的决定中都起着关键作用。这些过程控制关键转录因子的调控元件,从而建立不同细胞命运所特有的网络,并引发独特的转录事件浪潮。由于先前方法带来的技术挑战,很难通过染色质调控来解读早期胚胎发育过程中细胞命运决定的机制。最近,单细胞方法给发育生物学领域带来了变革,使人们能够以前所未有的视角了解分化过程中早期谱系分离事件中的染色质结构和相互作用。在这里,我们回顾了最近的技术进展以及它们如何加深了我们对早期分化事件中染色质调控的理解。