c-Myc controls the balance between hematopoietic stem cell self-renewal and differentiation.

Détails

ID Serval
serval:BIB_F61A299BA9AA
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
c-Myc controls the balance between hematopoietic stem cell self-renewal and differentiation.
Périodique
Genes and development
Auteur(s)
Wilson A., Murphy M.J., Oskarsson T., Kaloulis K., Bettess M.D., Oser G.M., Pasche A.C., Knabenhans C., Macdonald H.R., Trumpp A.
ISSN
0890-9369
Statut éditorial
Publié
Date de publication
2004
Peer-reviewed
Oui
Volume
18
Numéro
22
Pages
2747-2763
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
The activity of adult stem cells is essential to replenish mature cells constantly lost due to normal tissue turnover. By a poorly understood mechanism, stem cells are maintained through self-renewal while concomitantly producing differentiated progeny. Here, we provide genetic evidence for an unexpected function of the c-Myc protein in the homeostasis of hematopoietic stem cells (HSCs). Conditional elimination of c-Myc activity in the bone marrow (BM) results in severe cytopenia and accumulation of HSCs in situ. Mutant HSCs self-renew and accumulate due to their failure to initiate normal stem cell differentiation. Impaired differentiation of c-Myc-deficient HSCs is linked to their localization in the differentiation preventative BM niche environment, and correlates with up-regulation of N-cadherin and a number of adhesion receptors, suggesting that release of HSCs from the stem cell niche requires c-Myc activity. Accordingly, enforced c-Myc expression in HSCs represses N-cadherin and integrins leading to loss of self-renewal activity at the expense of differentiation. Endogenous c-Myc is differentially expressed and induced upon differentiation of long-term HSCs. Collectively, our data indicate that c-Myc controls the balance between stem cell self-renewal and differentiation, presumably by regulating the interaction between HSCs and their niche.
Mots-clé
Anemia/etiology, Animals, Bone Marrow/metabolism, Bone Marrow/pathology, Cadherins/metabolism, Cell Adhesion, Cell Differentiation, Cell Survival, Female, Hematopoiesis/physiology, Hematopoietic Stem Cells/cytology, Hematopoietic Stem Cells/metabolism, Humans, Integrases/metabolism, Integrins/metabolism, Mice, Mice, Inbred C57BL, Mice, Transgenic, Proto-Oncogene Proteins c-myc/genetics, Proto-Oncogene Proteins c-myc/physiology, RNA, Messenger/genetics, RNA, Messenger/metabolism, Receptors, Cell Surface/metabolism, Reverse Transcriptase Polymerase Chain Reaction, Up-Regulation
Pubmed
Web of science
Open Access
Oui
Création de la notice
09/02/2010 14:47
Dernière modification de la notice
20/08/2019 16:22
Données d'usage