Wnts are dispensable for differentiation and self-renewal of adult murine hematopoietic stem cells.
Blood
; 126(9): 1086-94, 2015 Aug 27.
Article
em En
| MEDLINE
| ID: mdl-26089398
ABSTRACT
Wnt signaling controls early embryonic hematopoiesis and dysregulated ß-catenin is implicated in leukemia. However, the role of Wnts and their source in adult hematopoiesis is still unclear, and is clinically important as upstream Wnt inhibitors enter clinical trials. We blocked Wnt secretion in hematopoietic lineages by targeting Porcn, a membrane-bound O-acyltransferase that is indispensable for the activity and secretion of all vertebrate Wnts. Surprisingly, deletion of Porcn in Rosa-CreER(T2)/Porcn(Del), MX1-Cre/Porcn(Del), and Vav-Cre/Porcn(Del) mice had no effects on proliferation, differentiation, or self-renewal of adult hematopoietic stem cells. Targeting Wnt secretion in the bone marrow niche by treatment with a PORCN inhibitor, C59, similarly had no effect on hematopoiesis. These results exclude a role for hematopoietic PORCN-dependent Wnts in adult hematopoiesis. Clinical use of upstream Wnt inhibitors is not likely to be limited by effects on hematopoiesis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Hematopoéticas
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Via de Sinalização Wnt
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Hematopoese
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article