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

Zahra Kabiri, Akihiko Numata, Akira Kawasaki, Edison, Daniel G. Tenen, David M. Virshup

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

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-CreERT2/PorcnDel, MX1-Cre/PorcnDel, and Vav-Cre/PorcnDel 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.

Original languageEnglish
Pages (from-to)1086-1094
Number of pages9
JournalBlood
Volume126
Issue number9
DOIs
Publication statusPublished - Aug 27 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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