| First Author | Quéré R | Year | 2014 |
| Journal | Proc Natl Acad Sci U S A | Volume | 111 |
| Issue | 29 | Pages | 10592-7 |
| PubMed ID | 25002492 | Mgi Jnum | J:212263 |
| Mgi Id | MGI:5578407 | Doi | 10.1073/pnas.1405546111 |
| Citation | Quere R, et al. (2014) Tif1gamma regulates the TGF-beta1 receptor and promotes physiological aging of hematopoietic stem cells. Proc Natl Acad Sci U S A 111(29):10592-7 |
| abstractText | 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. |
