Developmental dynamics of two bipotent thymic epithelial progenitor types

Nusser A, Sagar , Swann JB, Krauth B, Diekhoff D, Calderon L, Happe C, Gruen D, Boehm T (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Nature Nature Research

Book Volume: 606

Pages Range: 165-171

Journal Issue: 7912

DOI: 10.1038/s41586-022-04752-8

Abstract

T cell development in the thymus is essential for cellular immunity and depends on the organotypic thymic epithelial microenvironment. In comparison with other organs, the size and cellular composition of the thymus are unusually dynamic, as exemplified by rapid growth and high T cell output during early stages of development, followed by a gradual loss of functional thymic epithelial cells and diminished naive T cell production with age1–10. Single-cell RNA sequencing (scRNA-seq) has uncovered an unexpected heterogeneity of cell types in the thymic epithelium of young and aged adult mice11–18; however, the identities and developmental dynamics of putative pre- and postnatal epithelial progenitors have remained unresolved1,12,16,17,19–27. Here we combine scRNA-seq and a new CRISPR–Cas9-based cellular barcoding system in mice to determine qualitative and quantitative changes in the thymic epithelium over time. This dual approach enabled us to identify two principal progenitor populations: an early bipotent progenitor type biased towards cortical epithelium and a postnatal bipotent progenitor population biased towards medullary epithelium. We further demonstrate that continuous autocrine provision of Fgf7 leads to sustained expansion of thymic microenvironments without exhausting the epithelial progenitor pools, suggesting a strategy to modulate the extent of thymopoietic activity.

Involved external institutions

Max-Planck-Institut für Immunbiologie und Epigenetik (MPI-IE) / Max Planck Institute of Immunobiology and Epigenetics DE Germany (DE)

How to cite

APA:

Nusser, A., Sagar, ., Swann, J.B., Krauth, B., Diekhoff, D., Calderon, L.,... Boehm, T. (2022). Developmental dynamics of two bipotent thymic epithelial progenitor types. Nature, 606(7912), 165-171. https://doi.org/10.1038/s41586-022-04752-8

MLA:

Nusser, Anja, et al. "Developmental dynamics of two bipotent thymic epithelial progenitor types." Nature 606.7912 (2022): 165-171.

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