Tif1γ regulates the TGF-β1 receptor and promotes physiological aging of hematopoietic stem cells

Ronan Quéré*, Laetitia Saint-Paul, Virginie Carmignac, Romain Z. Martin, Marie Lorraine Chret́ien, Anne Largeot, Arlette Hammann, Jean Paul Pais De Barros, Jean Noël Bastie, Laurent Delva

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

49 Citations (Scopus)

Abstract

The hematopoietic system declines with age. Myeloid-biased differentiation and increased incidence of myeloid malignancies feature aging of hematopoietic stem cells (HSCs), but the mechanisms involved remain uncertain. Here, we report that 4-mo-old mice deleted for transcription intermediary factor 1γ (Tif1γ) in HSCs developed an accelerated aging phenotype. To reinforce this result, we also show that Tif1γ is down-regulated in HSCs during aging in 20-mo-old wild-type mice.We established that Tif1γ controls TGF-β1 receptor (Tgfbr1) turnover. Compared with young HSCs, Tif1γ-/- and old HSCs are more sensitive to TGF-β signaling. Importantly, we identified two populations of HSCs specifically discriminated by Tgfbr1 expression level and provided evidence of the capture of myeloid-biased (Tgfbr1hi) and myeloid-lymphoid-balanced (Tgfbr1 lo) HSCs. In conclusion, our data provide a new paradigm for Tif1γ in regulating the balance between lymphoid- and myeloid-derived HSCs through TGF-β signaling, leading to HSC aging.

Original languageEnglish
Pages (from-to)10592-10597
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number29
DOIs
Publication statusPublished - 22 Jul 2014
Externally publishedYes

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