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

Y Baba, T Yokota, H Spits, KP Garrett… - The journal of …, 2006 - journals.aai.org
Y Baba, T Yokota, H Spits, KP Garrett, SI Hayashi, PW Kincade
The journal of Immunology, 2006journals.aai.org
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-Kit low Sca-1 low/− 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 …
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-Kit low Sca-1 low/− 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 defined 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.
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