Hematopoietic stem cell function and survival depend on c-Myc and N-Myc activity.

Détails

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Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_C0E125BF99F7
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Hematopoietic stem cell function and survival depend on c-Myc and N-Myc activity.
Périodique
Cell stem cell
Auteur(s)
Laurenti E., Varnum-Finney B., Wilson A., Ferrero I., Blanco-Bose W.E., Ehninger A., Knoepfler P.S., Cheng P.F., MacDonald H.R., Eisenman R.N., Bernstein I.D., Trumpp A.
ISSN
1875-9777 ([electronic])
Statut éditorial
Publié
Date de publication
2008
Peer-reviewed
Oui
Volume
3
Numéro
6
Pages
611-624
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
Publication Status: ppublish
Résumé
Myc activity is emerging as a key element in acquisition and maintenance of stem cell properties. We have previously shown that c-Myc deficiency results in accumulation of defective hematopoietic stem cells (HSCs) due to niche-dependent differentiation defects. Here we report that immature HSCs coexpress c-myc and N-myc mRNA at similar levels. Although conditional deletion of N-myc in the bone marrow does not affect hematopoiesis, combined deficiency of c-Myc and N-Myc (dKO) results in pancytopenia and rapid lethality. Interestingly, proliferation of HSCs depends on both myc genes during homeostasis, but is c-Myc/N-Myc independent during bone marrow repair after injury. Strikingly, while most dKO hematopoietic cells undergo apoptosis, only self-renewing HSCs accumulate the cytotoxic molecule Granzyme B, normally employed by the innate immune system, thereby revealing an unexpected mechanism of stem cell apoptosis. Collectively, Myc activity (c-Myc and N-Myc) controls crucial aspects of HSC function including proliferation, differentiation, and survival.
Mots-clé
Animals, Cell Differentiation/genetics, Cell Lineage/genetics, Cell Proliferation, Cell Survival/genetics, Cells, Cultured, Graft Survival/genetics, Granzymes/metabolism, Hematopoiesis/physiology, Hematopoietic Stem Cell Transplantation/methods, Hematopoietic Stem Cells/cytology, Hematopoietic Stem Cells/metabolism, Mice, Mice, Knockout, Pancytopenia/genetics, Pancytopenia/physiopathology, Proto-Oncogene Proteins c-myc/genetics, Signal Transduction/genetics, Stress, Physiological/genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
09/02/2010 14:39
Dernière modification de la notice
09/05/2019 0:44
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