Developmental dynamics of two bipotent thymic epithelial progenitor types

Nusser, Anja; Sagar,; Swann, Jeremy; Krauth, Brigitte; Diekhoff, Dagmar; Calderon, Lesly; Happe, Christiane; Grün, Dominic; Boehm, Thomas

doi:10.1038/s41586-022-04752-8

Item

ITEM ACTIONSEXPORT

Add to Basket

Please note that a newer version of this item is available:
https://pure.mpg.de/pubman/item/item_3386481_2

DetailsSummary

Released

Journal Article

Developmental dynamics of two bipotent thymic epithelial progenitor types

MPS-Authors

/persons/resource/persons204351

Nusser, Anja
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Sagar,
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons191341

Swann, Jeremy
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Krauth, Brigitte
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Diekhoff, Dagmar
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Calderon, Lesly
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Happe, Christiane
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons241712

Grün, Dominic
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons190993

Boehm, Thomas
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

External Resource

https://www.nature.com/articles/s41586-022-04752-8
(Publisher version)

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

Nusser et al. 2022.pdf
(Publisher version), 23MB

Supplementary Material (public)

There is no public supplementary material available

Citation

Nusser, A., Sagar, Swann, J., Krauth, B., Diekhoff, D., Calderon, L., et al. (2022). Developmental dynamics of two bipotent thymic epithelial progenitor types. Nature. doi:10.1038/s41586-022-04752-8.

Cite as: https://hdl.handle.net/21.11116/0000-000A-8C1C-A

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 age. Single-cell RNA sequencing (scRNA-seq) has uncovered an unexpected heterogeneity of cell types in the thymic epithelium of young and aged adult mice; however, the identities and developmental dynamics of putative pre- and postnatal epithelial progenitors have remained unresolved. 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.