TY - JOUR
T1 - Tif1γ regulates the TGF-β1 receptor and promotes physiological aging of hematopoietic stem cells
AU - Quéré, Ronan
AU - Saint-Paul, Laetitia
AU - Carmignac, Virginie
AU - Martin, Romain Z.
AU - Chret́ien, Marie Lorraine
AU - Largeot, Anne
AU - Hammann, Arlette
AU - Pais De Barros, Jean Paul
AU - Bastie, Jean Noël
AU - Delva, Laurent
PY - 2014/7/22
Y1 - 2014/7/22
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84904642596&partnerID=8YFLogxK
U2 - 10.1073/pnas.1405546111
DO - 10.1073/pnas.1405546111
M3 - Article
C2 - 25002492
AN - SCOPUS:84904642596
SN - 0027-8424
VL - 111
SP - 10592
EP - 10597
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 29
ER -