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

Jennifer E. Cowan, Justin Malin, Yongge Zhao, Mina O. Seedhom, Christelle Harly, Izumi Ohigashi, Michael Kelly, Yousuke Takahama, Jonathan W. Yewdell, Maggie Cam and Avinash Bhandoola ()
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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

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-13465-y

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