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

Jennifer E CowanJustin MalinYongge ZhaoMina O SeedhomChristelle HarlyIzumi OhigashiMichael KellyYousuke TakahamaJonathan W YewdellMaggie CamAvinash Bhandoola
Published in: Nature communications (2019)
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.
Keyphrases
  • transcription factor
  • gene expression
  • poor prognosis
  • quality improvement
  • signaling pathway
  • genome wide
  • oxidative stress
  • long non coding rna
  • young adults
  • living cells
  • fluorescent probe