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

Nat Commun. 2019 Dec 2;10(1):5498. doi: 10.1038/s41467-019-13465-y.

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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism*
  • Female
  • Gene Expression Regulation, Developmental
  • Humans
  • Male
  • Mice
  • Mice, Transgenic
  • Oncogene Protein p55(v-myc) / genetics
  • Oncogene Protein p55(v-myc) / metabolism*
  • Organ Size
  • Organogenesis
  • Thymus Gland / embryology*
  • Thymus Gland / metabolism
  • Transcription, Genetic*

Substances

  • Oncogene Protein p55(v-myc)