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Wnts are dispensable for differentiation and self-renewal of adult murine hematopoietic stem cells.
Kabiri, Zahra; Numata, Akihiko; Kawasaki, Akira; Tenen, Daniel G; Virshup, David M.
Afiliación
  • Kabiri Z; Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore; Department of Biochemistry and.
  • Numata A; Cancer Science Institute, National University of Singapore, Singapore;
  • Kawasaki A; Cancer Science Institute, National University of Singapore, Singapore;
  • Edison; Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore;
  • Tenen DG; Cancer Science Institute, National University of Singapore, Singapore; Harvard Stem Cell Institute, Harvard Medical School, Boston, MA; and.
  • Virshup DM; Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore; Department of Biochemistry and Department of Pediatrics, Duke University School of Medicine, Durham, NC.
Blood ; 126(9): 1086-94, 2015 Aug 27.
Article en En | MEDLINE | ID: mdl-26089398
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.
Asunto(s)

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Células Madre Hematopoyéticas / Vía de Señalización Wnt / Hematopoyesis Límite: Animals Idioma: En Revista: Blood Año: 2015 Tipo del documento: Article

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Células Madre Hematopoyéticas / Vía de Señalización Wnt / Hematopoyesis Límite: Animals Idioma: En Revista: Blood Año: 2015 Tipo del documento: Article