CABLES1 Deficiency Impairs Quiescence and Stress Responses of Hematopoietic Stem Cells in Intrinsic and Extrinsic Manners - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Current Stem Cell Reports Année : 2019

CABLES1 Deficiency Impairs Quiescence and Stress Responses of Hematopoietic Stem Cells in Intrinsic and Extrinsic Manners

Résumé

Bone marrow (BM) niche cells help to keep adult hematopoietic stem cells (HSCs) in a quiescent state via secreted factors and induction of cell-cycle inhibitors. Here, we demonstrate that the adapter protein CABLES1 is a key regulator of long-term hematopoietic homeostasis during stress and aging. Young mice lacking Cables1 displayed hyperproliferation of hematopoietic progenitor cells. This defect was cell intrinsic, since it was reproduced in BM transplantation assays using wild-type animals as recipients. Overexpression and short hairpin RNA-mediated depletion of CABLES1 protein resulted in p21Cip/waf up- and downregulation, respectively. Aged mice lacking Cables1 displayed abnormalities in peripheral blood cell counts accompanied by a significant reduction in HSC compartment, concomitant with an increased mobilization of progenitor cells. In addition, Cables1-/- mice displayed increased sensitivity to the chemotherapeutic agent 5-fluorouracil due to an abnormal microenvironment. Altogether, our findings uncover a key role for CABLES1 in HSC homeostasis and stress hematopoiesis.
Fichier principal
Vignette du fichier
S2213671119302280.pdf (13.64 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-02380609 , version 1 (20-07-2022)

Licence

Paternité - Pas d'utilisation commerciale

Identifiants

Citer

Liang He, Florian Beghi, Viviane Baral, Mallorie Dépond, Yanyan Zhang, et al.. CABLES1 Deficiency Impairs Quiescence and Stress Responses of Hematopoietic Stem Cells in Intrinsic and Extrinsic Manners. Current Stem Cell Reports, 2019, 13 (2), pp.274-290. ⟨10.1016/j.stemcr.2019.06.002⟩. ⟨hal-02380609⟩
33 Consultations
3 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More