Wnts are dispensable for differentiation and self-renewal of adult murine hematopoietic stem cells.

Published

Journal Article

Wnt signaling controls early embryonic hematopoiesis and dysregulated β-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.

Full Text

Duke Authors

Cited Authors

  • Kabiri, Z; Numata, A; Kawasaki, A; Edison, ; Tenen, DG; Virshup, DM

Published Date

  • August 2015

Published In

Volume / Issue

  • 126 / 9

Start / End Page

  • 1086 - 1094

PubMed ID

  • 26089398

Pubmed Central ID

  • 26089398

Electronic International Standard Serial Number (EISSN)

  • 1528-0020

International Standard Serial Number (ISSN)

  • 0006-4971

Digital Object Identifier (DOI)

  • 10.1182/blood-2014-09-598540

Language

  • eng