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Developmental dynamics of two bipotent thymic epithelial progenitor types

Author

Listed:
  • Anja Nusser

    (Max Planck Institute of Immunobiology and Epigenetics)

  • Sagar

    (Max Planck Institute of Immunobiology and Epigenetics
    University Hospital Freiburg)

  • Jeremy B. Swann

    (Max Planck Institute of Immunobiology and Epigenetics)

  • Brigitte Krauth

    (Max Planck Institute of Immunobiology and Epigenetics)

  • Dagmar Diekhoff

    (Max Planck Institute of Immunobiology and Epigenetics)

  • Lesly Calderon

    (Max Planck Institute of Immunobiology and Epigenetics
    Institute of Molecular Pathology)

  • Christiane Happe

    (Max Planck Institute of Immunobiology and Epigenetics)

  • Dominic Grün

    (Max Planck Institute of Immunobiology and Epigenetics
    Max Planck Research Group at the Julius-Maximilians-Universität Würzburg
    Helmholtz Centre for Infection Research (HZI))

  • Thomas Boehm

    (Max Planck Institute of Immunobiology and Epigenetics
    University of Freiburg)

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.

Suggested Citation

  • Anja Nusser & Sagar & Jeremy B. Swann & Brigitte Krauth & Dagmar Diekhoff & Lesly Calderon & Christiane Happe & Dominic Grün & Thomas Boehm, 2022. "Developmental dynamics of two bipotent thymic epithelial progenitor types," Nature, Nature, vol. 606(7912), pages 165-171, June.
  • Handle: RePEc:nat:nature:v:606:y:2022:i:7912:d:10.1038_s41586-022-04752-8
    DOI: 10.1038/s41586-022-04752-8
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    Cited by:

    1. Xue Zhong & Nagesh Peddada & Jianhui Wang & James J. Moresco & Xiaowei Zhan & John M. Shelton & Jeffrey A. SoRelle & Katie Keller & Danielle Renee Lazaro & Eva Marie Y. Moresco & Jin Huk Choi & Bruce , 2023. "OVOL2 sustains postnatal thymic epithelial cell identity," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    2. Fabian Klein & Clara Veiga-Villauriz & Anastasiya Börsch & Stefano Maio & Sam Palmer & Fatima Dhalla & Adam E. Handel & Saulius Zuklys & Irene Calvo-Asensio & Lucas Musette & Mary E. Deadman & Andrea , 2023. "Combined multidimensional single-cell protein and RNA profiling dissects the cellular and functional heterogeneity of thymic epithelial cells," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. Yuki Takakura & Moeka Machida & Natsumi Terada & Yuka Katsumi & Seika Kawamura & Kenta Horie & Maki Miyauchi & Tatsuya Ishikawa & Nobuko Akiyama & Takao Seki & Takahisa Miyao & Mio Hayama & Rin Endo &, 2024. "Mitochondrial protein C15ORF48 is a stress-independent inducer of autophagy that regulates oxidative stress and autoimmunity," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    4. Beth Lucas & Andrea J. White & Fabian Klein & Clara Veiga-Villauriz & Adam Handel & Andrea Bacon & Emilie J. Cosway & Kieran D. James & Sonia M. Parnell & Izumi Ohigashi & Yousuke Takahama & William E, 2023. "Embryonic keratin19+ progenitors generate multiple functionally distinct progeny to maintain epithelial diversity in the adult thymus medulla," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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