β-catenin expression in the bone marrow microenvironment is required for long-term maintenance of primitive hematopoietic cells

Michael J. Nemeth, Kingston K. Mak, Yingzi Yang, David M. Bodine

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

61 Citations (Scopus)

Abstract

Hematopoiesis is dependent upon the bone marrow microenvironment, which is comprised of multiple mesenchymal cell types, including fibroblasts, endothelial cells, osteoblasts, and stroma progenitors. The canonical Wnt signaling pathway, which relies on the β-catenin protein to mediate its signal, is necessary for the normal development of mesenchymal tissue. We hypothesized that canonical Wnt signaling regulates the cellular composition and function of the bone marrow microenvironment. We observed that a β-catenin-deficient bone marrow microenvironment maintained hematopoietic stem cells but exhibited a decreased capacity to support primitive hematopoietic cells. These results correlated with decreased numbers of osteoblasts and with decreased production of basic fibroblast growth factor, stem cell factor, and vascular cell adhesion molecule-1. From these data, we propose a model in which β-catenin in the microenvironment is required noncell autonomously for long-term maintenance of hematopoietic progenitors. © AlphaMed Press.
Original languageEnglish
Pages (from-to)1109-1119
JournalStem Cells
Volume27
Issue number5
DOIs
Publication statusPublished - May 2009
Externally publishedYes

Bibliographical note

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Research Keywords

  • Hematopoietic stem cells
  • Myeloid progenitor cells
  • Transgenic mice
  • Wnt

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