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

Hematopoietic stem cell aging has been directly linked to the development of several hematological disorders, including myeloproliferative diseases. Here we show that in elderly mice (20 mo old), physiological aging of the hematopoietic system is linked to a decreased expression of transcription intermediary factor 1γ (Tif1γ) in HSCs. In turn, in young Tif1γ^-/- mice (4 mo old), the hematopoiesis aging phenotype is exacerbated. In both sets of mice, Tif1γ level controls the TGF-β receptor 1 (Tgfbr1) turnover and subtly regulates the number of myeloid-biased HSCs in bone marrow. We establish that young Tif1γ^-/- mice develop a phenotype of premature hematopoietic aging that may explain their predisposition to myeloproliferative disease.