Speed and navigation control of thymocyte development by the fetal T-cell gene regulatory network
- Creators
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MacNabb, Brendan W.
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Rothenberg, Ellen V.
Abstract
T-cell differentiation is a tightly regulated developmental program governed by interactions between transcription factors (TFs) and chromatin landscapes and affected by signals received from the thymic stroma. This process is marked by a series of checkpoints: T-lineage commitment, T-cell receptor (TCR)β selection, and positive and negative selection. Dynamically changing combinations of TFs drive differentiation along the T-lineage trajectory, through mechanisms that have been most extensively dissected in adult mouse T-lineage cells. However, fetal T-cell development differs from adult in ways that suggest that these TF mechanisms are not fully deterministic. The first wave of fetal T-cell differentiation occurs during a unique developmental window during thymic morphogenesis, shows more rapid kinetics of differentiation with fewer rounds of cell division, and gives rise to unique populations of innate lymphoid cells (ILCs) and invariant γδT cells that are not generated in the adult thymus. As the characteristic kinetics and progeny biases are cell-intrinsic properties of thymic progenitors, the differences could be based on distinct TF network circuitry within the progenitors themselves. Here, we review recent single-cell transcriptome data that illuminate the TF networks involved in T-cell differentiation in the fetal and adult mouse thymus.
Copyright and License
© 2023 John Wiley & Sons.
Acknowledgement
The authors would like to thank Boyoung Shin for helpful advice on data analysis, Samantha Chang for critical reading of the manuscript, and our developmental biology colleagues at Caltech for stimulating interchange about dynamical developmental systems. Research support for the authors came from a USPHS grant to E.V.R., R01 HD100039. E.V.R. also gratefully acknowledges support from the Edward B. Lewis Professorship in Biology.
Contributions
B. W. M. designed the project, carried out the literature search and data analysis, and wrote drafts and edited the paper. E. V. R. conceived of the project and advised on the project, added to the literature search, contributed to the drafts, and edited the paper.
Data Availability
All data described in this review article are already published and available from public repositories. The manuscript provides Gene Expression Omnibus accession numbers for all data sets used.
Conflict of Interest
B. W. M. declares no competing interests. E. V. R. has been a member of the Scientific Advisory Board of Century Therapeutics, and has advised for Kite Pharma and A2 Biotherapeutics.
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Additional details
- Eprint ID
- 119563
- Resolver ID
- CaltechAUTHORS:20230227-88449200.51
- PMCID
- PMC10771342
- DOI
- 10.1111/imr.13190
- Edward B. Lewis Professorship of Biology
- National Institutes of Health
- R01HD100039
- Created
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2023-05-04Created from EPrint's datestamp field
- Updated
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2023-05-04Created from EPrint's last_modified field
- Caltech groups
- Division of Biology and Biological Engineering