Tif1gamma regulates the TGF-beta1 receptor and promotes physiological aging of hematopoietic stem cells.

Fiche publication


Date publication

juillet 2014

Auteurs

Membres identifiés du Cancéropôle Est :
Pr BASTIE Jean-Noël, Dr DELVA Laurent, Dr PAIS DE BARROS Jean-Paul, Dr QUERE Ronan, Dr CHRETIEN Marie-Lorraine


Tous les auteurs :
Quere R, Saint-Paul L, Carmignac V, Martin RZ, Chretien ML, Largeot A, Hammann A, Pais de Barros JP, Bastie JN, Delva L

Résumé

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 1gamma (Tif1gamma) in HSCs developed an accelerated aging phenotype. To reinforce this result, we also show that Tif1gamma is down-regulated in HSCs during aging in 20-mo-old wild-type mice. We established that Tif1gamma controls TGF-beta1 receptor (Tgfbr1) turnover. Compared with young HSCs, Tif1gamma(-/-) and old HSCs are more sensitive to TGF-beta signaling. Importantly, we identified two populations of HSCs specifically discriminated by Tgfbr1 expression level and provided evidence of the capture of myeloid-biased (Tgfbr1(hi)) and myeloid-lymphoid-balanced (Tgfbr1(lo)) HSCs. In conclusion, our data provide a new paradigm for Tif1gamma in regulating the balance between lymphoid- and myeloid-derived HSCs through TGF-beta signaling, leading to HSC aging.

Référence

Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):10592-7