Tif1γ regulates the TGF-β1 receptor and promotes physiological aging of hematopoietic stem cells.
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 specifical…
Symplekin, a polyadenylation factor, prevents MOZ and MLL activity on HOXA9 in hematopoietic cells
International audience; MOZ and MLL encoding a histone acetyltransferase and a histone methyltransferase, respectively, are targets for recurrent chromosomal translocations found in acute myeloblastic or lymphoblastic leukemia. We have previously shown that MOZ and MLL cooperate to activate HOXA9 gene expression in hematopoietic stem/progenitors cells. To dissect the mechanism of action of this complex, we decided to identify new proteins interacting with MOZ. We found that the scaffold protein Symplekin that supports the assembly of polyadenylation machinery was identified by mass spectrometry. Symplekin interacts and co-localizes with both MOZ and MLL in immature hematopoietic cells. Its …
Un nouveau modèle murin du vieillissement de l’hématopoïèse
Un nouveau modele murin du vieillissement de l’hematopoiese Ronan Quere 1,2, Jean-Noel Bastie1,2,3, Laurent Delva1,2 1 Inserm, UMR 866, faculte de medecine, universite de Bourgogne, 7 boulevard Jeanne d’Arc, 21000 Dijon, France ; 2 Labex LipSTIC, universite de Bourgogne, 21000 Dijon, France ; 3 hopital universitaire, service d’hematologie clinique, 21000 Dijon, France. ronan.quere@inserm.fr laurent.delva@u-bourgogne.fr