title: Tif1γ regulates the TGF-β1 receptor and promotes physiological aging of hematopoietic stem cells.
abstract: 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 myeloid-derived HSCs through TGF-β signaling, leading to HSC aging.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale UMR866, 21000 Dijon, France;Labex LipSTIC and laurent.delva@u-bourgogne.fr ronan.quere@inserm.fr.
authors.forename: Ronan
authors.initials: R
authors.lastname: Quéré
authors.affiliation: Institut National de la Santé et de la Recherche Médicale UMR866, 21000 Dijon, France;Labex LipSTIC and.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Saint-Paul
authors.affiliation: Equipe Génétique des Anomalies du Développement, EA 4271, Université de Bourgogne, 21000 Dijon, France;
authors.forename: Virginie
authors.initials: V
authors.lastname: Carmignac
authors.affiliation: Institut National de la Santé et de la Recherche Médicale UMR866, 21000 Dijon, France;Labex LipSTIC and.
authors.forename: Romain Z
authors.initials: RZ
authors.lastname: Martin
authors.affiliation: Institut National de la Santé et de la Recherche Médicale UMR866, 21000 Dijon, France;Labex LipSTIC andHôpital Universitaire, Service d'Hématologie Clinique, 21000 Dijon, France; and.
authors.forename: Marie-Lorraine
authors.initials: ML
authors.lastname: Chrétien
authors.affiliation: Institut National de la Santé et de la Recherche Médicale UMR866, 21000 Dijon, France;Labex LipSTIC and.
authors.forename: Anne
authors.initials: A
authors.lastname: Largeot
authors.affiliation: Plateforme de cytométrie and.
authors.forename: Arlette
authors.initials: A
authors.lastname: Hammann
authors.affiliation: Plateforme de lipidomique, Université de Bourgogne, 21000 Dijon, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Pais de Barros
authors.affiliation: Institut National de la Santé et de la Recherche Médicale UMR866, 21000 Dijon, France;Labex LipSTIC andHôpital Universitaire, Service d'Hématologie Clinique, 21000 Dijon, France; and.
authors.forename: Jean-Noël
authors.initials: JN
authors.lastname: Bastie
authors.affiliation: Institut National de la Santé et de la Recherche Médicale UMR866, 21000 Dijon, France;Labex LipSTIC and laurent.delva@u-bourgogne.fr ronan.quere@inserm.fr.
authors.forename: Laurent
authors.initials: L
authors.lastname: Delva
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002469:Cell Separation; D016922:Cellular Senescence / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D022423:Myeloid Cells / Q000378:metabolism; D010641:Phenotype; D025821:Polyubiquitin / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D011956:Receptors, Cell Surface / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D054875:Ubiquitination / Q000187:drug effects
chemical_list: D015703:Antigens, CD; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; C491420:Trim33 protein, mouse; D025821:Polyubiquitin; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625842:Tgfbr1 protein, mouse