期刊
BIOESSAYS
卷 43, 期 5, 页码 -出版社
WILEY
DOI: 10.1002/bies.202000345
关键词
cell fate decision; early T cell development; Notch signal; Runx factors; stage‐ specific action; transcription factor network
资金
- SENSHIN Medical Research Foundation
- Yasuda Memorial Medical Foundation
- Takeda Science Foundation
- Tokai University School of Medicine Research Aid
- UeharaMemorial Foundation
- Japan Society for the Promotion of Science [JP19H03692]
- Tokyo Biochemical Research Foundation
- Daiichi Sankyo Foundation of Life Science
- Princess Takamatsu CancerResearch Fund
- Naito Foundation
The establishment of cell lineage identity from multipotent progenitors is controlled by a combination of lineage-specific transcription factors, stably expressed transcription factors, and environmental signals. Recent advances in technical analysis have revealed unexpected mechanisms underlying the actions of transcription factors in cell fate decisions. In the context of early T cell development in the thymus, stable and continuously required factors like Notch and Runx family members play a crucial role in regulating the acquisition of T lineage identity.
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.
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