e-Article
CABLES1 Deficiency Impairs Quiescence and Stress Responses of Hematopoietic Stem Cells in Intrinsic and Extrinsic Manners.
Document Type
Academic Journal
Author
He L; Institut National de la Santé et de la Recherche Médicale, Inserm UMRS1170, 114 Rue Edouard Vaillant, 94805 Villejuif, France; Paris-Saclay University, Villejuif, France; Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France; Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.; Beghi F; Institut National de la Santé et de la Recherche Médicale, Inserm UMRS1170, 114 Rue Edouard Vaillant, 94805 Villejuif, France; Paris-Saclay University, Villejuif, France; Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.; Baral V; Institut National de la Santé et de la Recherche Médicale, Inserm UMRS1170, 114 Rue Edouard Vaillant, 94805 Villejuif, France; Paris-Saclay University, Villejuif, France; Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.; Dépond M; Institut National de la Santé et de la Recherche Médicale, Inserm UMRS1170, 114 Rue Edouard Vaillant, 94805 Villejuif, France; Paris-Saclay University, Villejuif, France; Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.; Zhang Y; Institut National de la Santé et de la Recherche Médicale, Inserm UMRS1170, 114 Rue Edouard Vaillant, 94805 Villejuif, France; Paris-Saclay University, Villejuif, France; Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.; Joulin V; Institut National de la Santé et de la Recherche Médicale, Inserm UMRS1170, 114 Rue Edouard Vaillant, 94805 Villejuif, France; Paris-Saclay University, Villejuif, France; Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.; Rueda BR; Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, USA.; Gonin P; Plateforme d'Evaluation Préclinique, AMMICA UMS 3655/ US 23, Gustave Roussy, Villejuif, France.; Foudi A; Paris-Saclay University, UFR Medicine, INSERM UMS 33, Andre Lwoff Institute, Paul Brousse Hospital, Villejuif, France.; Wittner M; Institut National de la Santé et de la Recherche Médicale, Inserm UMRS1170, 114 Rue Edouard Vaillant, 94805 Villejuif, France; Paris-Saclay University, Villejuif, France; Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France; CNRS, GDR 3697 MicroNiT, Tours, France.; Louache F; Institut National de la Santé et de la Recherche Médicale, Inserm UMRS1170, 114 Rue Edouard Vaillant, 94805 Villejuif, France; Paris-Saclay University, Villejuif, France; Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France; CNRS, GDR 3697 MicroNiT, Tours, France. Electronic address: fawzia.louache@gustaveroussy.fr.
Source
Publisher: Cell Press Country of Publication: United States NLM ID: 101611300 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2213-6711 (Electronic) Linking ISSN: 22136711 NLM ISO Abbreviation: Stem Cell Reports Subsets: MEDLINE
Subject
Language
English
Abstract
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 p21 Cip/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.
(Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
(Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)