Hematopoietic Stem Cell Function and Skeletal Formation: Positive Role of Hemp Gene
Hematopoietic stem cells (HSCs) have a capacity to undergo self-renewal and differentiation into several distinct cell lineages, which maintain blood production and provide mature blood cells throughout life. To clarify molecular mechanisms governing HSC development, we performed a genome-wide gene expression analysis of fetal liver (FL) HSC cDNA library, and identified a novel gene, hemp (h ematopoietic e xpressed m ammalian p olycomb), that encodes a protein with a zinc-finger domain and four malignant brain tumor (mbt) repeats. To elucidate its biological role(s), we generated hemp-deficient mice and found that Hemp plays pivotal roles in HSC function and skeletal formation. Mononuclear cell number in hemp −/− FLs was markedly reduced, and hemp −/− FL HSCs exhibited significant defects in colony-forming and competitive repopulation assays. In addition, hemp −/− embryos exhibited various skeletal malformations, such as a fusion of cervical vertebrae. Since osteoblasts and HSCs coexist in the bone marrow niche and physically and functionally interact with each other, it is suggested that Hemp-mediated signalling positively and coordinately regulates normal development of these types of cells. In addition, skeletal abnormalities detected in hemp −/− mice closely resemble to those observed in human Klippel-Feil anomaly, suggesting that Hemp might be involved in the pathogenesis of this disease.
KeywordsFetal Liver Malignant Brain Tumor Skeletal Abnormality Bone Marrow Niche Skeletal Formation
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