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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Tif1γ regulates the TGF-β1 receptor and promotes physiological aging of hematopoietic stem cells
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Tif1γ regulates the TGF-β1 receptor and promotes physiological aging of hematopoietic stem cells

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

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摘要

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 (Tgfbr1~(hi)) and myeloid-lymphoid-balanced (Tgfbr1~(lo)) HSCs. In conclusion, our data provide a new paradigm for Tif1γ in regulating the balance between lymphoid- and myeloidderived HSCs through TGF-β signaling, leading to HSC aging.

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