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Myc controls a distinct transcriptional program in fetal thymic epithelial cells that determines thymus growth

Author

Listed:
  • Jennifer E. Cowan

    (National Cancer Institute, National Institutes of Health)

  • Justin Malin

    (National Cancer Institute, National Institutes of Health)

  • Yongge Zhao

    (National Cancer Institute, National Institutes of Health)

  • Mina O. Seedhom

    (National Institutes of Health)

  • Christelle Harly

    (National Cancer Institute, National Institutes of Health)

  • Izumi Ohigashi

    (University of Tokushima)

  • Michael Kelly

    (National Cancer Institute, National Institutes of Health)

  • Yousuke Takahama

    (National Cancer Institute, National Institutes of Health)

  • Jonathan W. Yewdell

    (National Institutes of Health)

  • Maggie Cam

    (National Cancer Institute, National Institutes of Health)

  • Avinash Bhandoola

    (National Cancer Institute, National Institutes of Health)

Abstract

Interactions between thymic epithelial cells (TEC) and developing thymocytes are essential for T cell development, but molecular insights on TEC and thymus homeostasis are still lacking. Here we identify distinct transcriptional programs of TEC that account for their age-specific properties, including proliferation rates, engraftability and function. Further analyses identify Myc as a regulator of fetal thymus development to support the rapid increase of thymus size during fetal life. Enforced Myc expression in TEC induces the prolonged maintenance of a fetal-specific transcriptional program, which in turn extends the growth phase of the thymus and enhances thymic output; meanwhile, inducible expression of Myc in adult TEC similarly promotes thymic growth. Mechanistically, this Myc function is associated with enhanced ribosomal biogenesis in TEC. Our study thus identifies age-specific transcriptional programs in TEC, and establishes that Myc controls thymus size.

Suggested Citation

  • Jennifer E. Cowan & Justin Malin & Yongge Zhao & Mina O. Seedhom & Christelle Harly & Izumi Ohigashi & Michael Kelly & Yousuke Takahama & Jonathan W. Yewdell & Maggie Cam & Avinash Bhandoola, 2019. "Myc controls a distinct transcriptional program in fetal thymic epithelial cells that determines thymus growth," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13465-y
    DOI: 10.1038/s41467-019-13465-y
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    Cited by:

    1. 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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