PTH Regulates the Hematopoietic Stem Cell Niche in Bone
In late fetal life, hematopoiesis moves from the liver to the bone marrow in mammals, and continues to occur throughout postnatal life, with extramedullary hematopoiesis occurring only when disease blocks hematopoiesis in the marrow. Hematopoietic stem cells (HSCs) are uniquely the cells that can generate cells of all hematopoietic lineages. These cells do so by balancing an ability to increase their number by proliferation while staying pleuripotent (self-renewal) with their ability to differentiate into any of the hematopoietic lineages. Hematopoietic stem cells also happen to be able to circulate in the systemic circulation, a property likely to be important in their normal function. One of the reasons that we have learned so much about hematopoietic stem cells is that their properties underlie the ability of transplanted bone marrow to populate the marrow of patient recipients with failing bone marrow.
Clearly, the regulation of stem cell self-renewal and differentiation is crucial for normal function. A powerful idea that organizes a number of important properties of this regulation is that of the stem cell niche (Ohlstein, Kai, Decotto, et al. 2004; Scadden 2006). A niche is a particular place at which cells and matrix coalesce to regulate stem cells. This concept provides a source of the obvious need for paracrine regulation of stem cell properties. By providing a saturable number of sites for stem cell self-renewal, the niche also suggests a specific regulatory process: stem cells can enter and leave a niche and thus move toward or away from a unique site at which self renewal is possible. A recent series of advances has shown that hematopoietic stem cells can be found adjacent to both osteoblastic cells and endothelial cells in normal bone (Zhang, Niu, Ye, et al. 2003; Kiel, Yilmaz, Iwashita, et al. 2005). Here I will describe how activation of the PTH/PTHrP receptor found on cells of the osteoblast lineage can modify the niche for hematopoietic stem cells in bone in a way that allows such cells to accumulate in the marrow (Calvi, Adams, Weibrecht, et al. 2003). These findings have implications both for the normal regulation of hematopoiesis and for potential therapies in humans needing transplantation of human hematopoietic stem cells.
KeywordsHematopoietic Stem Cell Osteoblastic Cell Stem Cell Niche Fail Bone Marrow Hematopoietic Lineage
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