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


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.

SUBMITTER: Cowan JE 

PROVIDER: S-EPMC6889275 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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

Cowan Jennifer E JE   Malin Justin J   Zhao Yongge Y   Seedhom Mina O MO   Harly Christelle C   Harly Christelle C   Ohigashi Izumi I   Kelly Michael M   Takahama Yousuke Y   Yewdell Jonathan W JW   Cam Maggie M   Bhandoola Avinash A  

Nature communications 20191202 1


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 M  ...[more]

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