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

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, includi...

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Detalles Bibliográficos
Autores principales: Cowan, Jennifer E., Malin, Justin, Zhao, Yongge, Seedhom, Mina O., Harly, Christelle, Ohigashi, Izumi, Kelly, Michael, Takahama, Yousuke, Yewdell, Jonathan W., Cam, Maggie, Bhandoola, Avinash
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889275/
https://www.ncbi.nlm.nih.gov/pubmed/31792212
http://dx.doi.org/10.1038/s41467-019-13465-y
Descripción
Sumario: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.