Constitutively active β-catenin promotes expansion of multipotent hematopoietic progenitors in culture

Yoshihiro Baba, Takafumi Yokota, Hergen Spits, Karla P. Garrett, Shin Ichi Hayashi, Paul W. Kincade

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48 Citations (Scopus)

Abstract

This study was designed to investigate one component of the Wnt/β-catenin signaling pathway that has been implicated in stem cell self-renewal. Retroviral-mediated introduction of stable β-catenin to primitive murine bone marrow cells allowed the expansion of multipotential c-KitlowSca-1low/-CD19- CD11b/Mac-1 -Flk-2-CD43+AA4.1 +NK1.1+CD3-CD11c-Gr-1 -CD45R/B220+ cells in the presence of stromal cells and cytokines. They generated myeloid, T, and B lineage lymphoid cells in culture, but had no T lymphopoietic potential when transplanted. Stem cell factor and IL-6 were found to be minimal requirements for long-term, stromal-free propagation, and a β-catenin-transduced cell line was maintained for 5 mo with these denned conditions. Although multipotential and responsive to many normal stimuli in culture, it was unable to engraft several types of irradiated recipients. These findings support previous studies that have implicated the canonical Wnt pathway signaling in regulation of multipotent progenitors. In addition, we demonstrate how it may be experimentally manipulated to generate valuable cell lines.

Original languageEnglish
Pages (from-to)2294-2303
Number of pages10
JournalJournal of Immunology
Volume177
Issue number4
DOIs
Publication statusPublished - Aug 15 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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