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Nestin-expressing cells important in carving out the HSC niche
DOI:10.1038/bonekey.2014.122
Cells expressing nestin are known to support hematopoiesis in the bone marrow of adult mice. Ono et al. studied the endochrondal bones of mouse embryos expressing green fluorescent protein (GFP) under the control of a promoter/enhancer of nestin to try to understand how nestin-positive (Nes+) cells arise during development of the hematopoietic stem cell niche (HSC niche).
Endothelial and non-endothelial Nes+ cells were observed in the perichondrium of the embryos and their numbers expanded during endochrondal ossification and vascular invasion. Some of the Nes+ cells were found to be osterix-expressing osteoblast precursors, which are constantly replaced as bone growth occurs.
Experiments with transgenic mice revealed that Indian hedgehog (Ihh) and Runx2 were needed to generate non-endothelial Nes+ cells from their direct mesenchymal precursors. Some of these cells differentiate into preosteoblasts expressing osterix; others become endothelial cells, osteocytes, chondrocytes or stromal cells.
A second paper published concurrently by the same group reveals three waves of stromal cell development in which cells expressing osterix populate and organize the developing bone marrow. Notably, osterix+ cells within the developing embryo differentiate into long-lived bone marrow stromal cells and Nes+ osteoprecursors.
Editor’s comment: The authors demonstrate that all cell types that constitute the HSC niche, including endosteal osteoblasts, endothelial cells, pericytes and perivascular stromal cells, express nestin. Furthermore, nestin is expressed downstream of Ihh and Runx2. Thus, both endothelial and non-endothelial nestin-expressing cells are important components of the HSC niche.
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