Department of Immunology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Institute of Medical Sciences, Tokai University, Isehara, Kanagawa, Japan.
Bioessays. 2021 May;43(5):e2000345. doi: 10.1002/bies.202000345. Epub 2021 Feb 24.
Establishment of cell lineage identity from multipotent progenitors is controlled by cooperative actions of lineage-specific and stably expressed transcription factors, combined with input from environmental signals. Lineage-specific master transcription factors activate and repress gene expression by recruiting consistently expressed transcription factors and chromatin modifiers to their target loci. Recent technical advances in genome-wide and multi-omics analysis have shed light on unexpected mechanisms that underlie more complicated actions of transcription factors in cell fate decisions. In this review, we discuss functional dynamics of stably expressed and continuously required factors, Notch and Runx family members, throughout developmental stages of early T cell development in the thymus. Pre- and post-commitment stage-specific transcription factors induce dynamic redeployment of Notch and Runx binding genomic regions. Thus, together with stage-specific transcription factors, shared transcription factors across distinct developmental stages regulate acquisition of T lineage identity.
多能祖细胞向细胞谱系分化的建立受谱系特异性和稳定表达的转录因子的协同作用控制,同时还受到环境信号的输入影响。谱系特异性的主转录因子通过招募持续表达的转录因子和染色质修饰因子到其靶基因座来激活和抑制基因表达。最近在全基因组和多组学分析方面的技术进步揭示了意想不到的机制,这些机制为转录因子在细胞命运决定中的更复杂作用提供了基础。在这篇综述中,我们讨论了 Notch 和 Runx 家族成员在胸腺早期 T 细胞发育的各个发育阶段中稳定表达和持续需要的功能动态。在承诺前和承诺后阶段特异性转录因子诱导 Notch 和 Runx 结合基因组区域的动态重新配置。因此,与阶段特异性转录因子一起,不同发育阶段共有的转录因子调节 T 细胞谱系身份的获得。