Constitutively active beta-catenin promotes expansion of multipotent hematopoietic progenitors in culture.
This study was designed to investigate one component of the Wnt/beta-catenin signaling pathway that has been implicated in stem cell self-renewal. Retroviral-mediated introduction of stable beta-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 beta-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.
Baba
Yoshihiro
Y
Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA.
Yokota
Takafumi
T
Spits
Hergen
H
Garrett
Karla P
KP
Hayashi
Shin-Ichi
S
Kincade
Paul W
PW
D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D039902:Multipotent Stem Cells / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D051176:beta Catenin / Q000502:physiology*
D051176:beta Catenin