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


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
02 12 2019
Historique:
received: 03 05 2019
accepted: 11 11 2019
entrez: 4 12 2019
pubmed: 4 12 2019
medline: 5 3 2020
Statut: epublish

Résumé

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.

Identifiants

pubmed: 31792212
doi: 10.1038/s41467-019-13465-y
pii: 10.1038/s41467-019-13465-y
pmc: PMC6889275
doi:

Substances chimiques

Oncogene Protein p55(v-myc) 0

Types de publication

Journal Article Research Support, N.I.H., Intramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

5498

Subventions

Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : 1 ZIA BC011633
Pays : International

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Auteurs

Jennifer E Cowan (JE)

Laboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.

Justin Malin (J)

Laboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.

Yongge Zhao (Y)

Laboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.

Mina O Seedhom (MO)

Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.

Christelle Harly (C)

Laboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.

Izumi Ohigashi (I)

Division of Experimental Immunology, Institute of Advanced Medical Sciences, University of Tokushima, Tokushima, 770-8503, Japan.

Michael Kelly (M)

Single Cell Analysis Facility, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.

Yousuke Takahama (Y)

Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.

Jonathan W Yewdell (JW)

Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.

Maggie Cam (M)

Office of Science and Technology Resources, Office of the Director, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.

Avinash Bhandoola (A)

Laboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. avinash.bhandoola@nih.gov.

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Classifications MeSH