Hematopoietic Stem Cell Function and Skeletal Formation: Positive Role of Hemp Gene

Chapter
Part of the Stem Cells and Cancer Stem Cells book series (STEM, volume 9)

Abstract

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.

Keywords

Fetal Liver Malignant Brain Tumor Skeletal Abnormality Bone Marrow Niche Skeletal Formation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Department of Disease Model, Research Institute of Radiation Biology and MedicineHiroshima UniversityMinami-ku, HiroshimaJapan

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