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  Developmental dynamics of two bipotent thymic epithelial progenitor types

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.

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Nusser et al. 2022.pdf (Publisher version), 23MB
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 Creators:
Nusser, Anja1, Author              
Sagar2, Author
Swann, Jeremy1, Author              
Krauth, Brigitte1, Author
Diekhoff, Dagmar1, Author
Calderon, Lesly1, Author
Happe, Christiane1, Author
Grün, Dominic2, Author              
Boehm, Thomas1, Author              
Affiliations:
1Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243647              
2Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243642              

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 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.

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Language(s): eng - English
 Dates: 2022-05-25
 Publication Status: Published online
 Pages: -
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 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41586-022-04752-8
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Title: Nature
  Abbreviation : Nature
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: - Sequence Number: - Start / End Page: - Identifier: ISSN: 0028-0836
CoNE: https://pure.mpg.de/cone/journals/resource/954925427238