Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 287, Issue 35, Pages 29979-29987Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M112.383018
Keywords
-
Categories
Funding
- National Institutes of Health [1R03HD064617]
- Department of Defense
- American Cancer Society
- Brigham and Women's Hospital
Ask authors/readers for more resources
Mechanisms that regulate proliferation and expansion of human hematopoietic stem/multipotent progenitor cells (HSC/MPPs) are targets of intensive investigations. Several cell intrinsic factors and signaling pathways have been implicated in the proliferation and differentiation of human HSC/MPPs. Nevertheless, expansion of human HSC/MPPs for clinical application remains a critical challenge. VentX is a human homeobox transcription factor that was recently identified as an anti-proliferation and pro-differentiation factor in human hematopoietic cells. Here, we report that VentX expression is up-regulated during ontogenesis of human hematopoietic cells. Strikingly, suppression of VentX expression led to significant expansion of HSC/MPPs ex vivo and a 20-fold increase in engraftment potential in the NOD/SCID/IL2R gamma 2(null) mouse model. VentX suppression helped preserve the HSC/MPP pools and promote clonogenicity of hematopoietic progenitor cells. Mechanistically, we show that VentX regulates critical cell cycle regulators and Wnt downstream genes previously implicated in HSC/MPP proliferation and expansion.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available