Transcriptional network dynamics in early T cell development
Abstract
The rate at which cells enter the T cell pathway depends not only on the immigration of hematopoietic precursors into the strong Notch signaling environment of the thymus but also on the kinetics with which each individual precursor cell reaches T-lineage commitment once it arrives. Notch triggers a complex, multistep gene regulatory network in the cells in which the steps are stereotyped but the transition speeds between steps are variable. Progenitor-associated transcription factors delay T-lineage differentiation even while Notch-induced transcription factors within the same cells push differentiation forward. Progress depends on regulator cross-repression, on breaching chromatin barriers, and on shifting, competitive collaborations between stage-specific and stably expressed transcription factors, as reviewed here.
Copyright and License
© 2024 Shin et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
Conflict of Interest
Disclosures: E.V. Rothenberg was on the Scientific Advisory Board for Century Therapeutics, Inc. until January 2023. The advisory work that she did for them does not have any overlap with material in the present article. The other authors have no disclosures to report.
Funding
Support was provided by US Public Health Service grants R01AI151704, R01AI135200, R01AI178114, and R01HD100039 to E.V. Rothenberg, a Caltech Postdoctoral Baxter Foundation Fellowship to B. Shin, a National Institutes of Health fellowship F32AI181504 to B.W. MacNabb, and the E.B. Lewis Professorship in Biology to E.V. Rothenberg.
Contributions
Author contributions: B. Shin: Conceptualization, Visualization, Writing—original draft, Writing—review & editing, S.J. Chang: Conceptualization, Data curation, Validation, Visualization, Writing—original draft, Writing—review & editing, B.W. MacNabb: Conceptualization, Writing—original draft, Writing—review & editing, E.V. Rothenberg: Conceptualization, Funding acquisition, Project administration, Supervision, Validation, Visualization, Writing—original draft, Writing—review & editing.
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Additional details
- ISSN
- 1540-9538
- United States Public Health Service
- R01AI151704
- United States Public Health Service
- R01AI135200
- United States Public Health Service
- R01AI178114
- United States Public Health Service
- R01HD100039
- Caltech Postdoctoral Baxter Foundation
- National Institutes of Health
- F32AI181504
- Accepted
-
2024-07-10Accepted
- Caltech groups
- Division of Biology and Biological Engineering