Speed and navigation control of thymocyte development by the fetal T-cell gene regulatory network.

Autor: MacNabb BW; Division of Biology & Biological Engineering, California Institute of Technology, Pasadena, California, USA., Rothenberg EV; Division of Biology & Biological Engineering, California Institute of Technology, Pasadena, California, USA.
Jazyk: angličtina
Zdroj: Immunological reviews [Immunol Rev] 2023 May; Vol. 315 (1), pp. 171-196. Date of Electronic Publication: 2023 Feb 01.
DOI: 10.1111/imr.13190
Abstrakt: 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.
(© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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