Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor

被引：515

作者：

Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States ^{[1
]}

不详 ^{[2
]}

不详 ^{[3
]}

不详 ^{[4
]}

不详 ^{[5
]}

不详 ^{[6
]}

机构：

[1] Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston

[2] Blood Transfusion Service, Massachusetts General Hospital, Harvard Medical School, Boston

[3] Harvard Stem Cell Institute, Harvard University, Cambridge

[4] Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston

[5] Endocrine-Hypertension Division, Brigham and Women's Hospital, Harvard Medical School, Boston

[6] Department of Pathology, Dartmouth-Hitchcock Medical Center, Dartmouth Medical School, Lebanon

来源：

Nature | 2006年 / 7076卷 / 599-603期

基金：

美国国家卫生研究院;

关键词：

Biological organs;

D O I：

10.1038/nature04247

中图分类号：

学科分类号：

摘要：

During mammalian ontogeny, haematopoietic stem cells (HSCs) translocate from the fetal liver to the bone marrow, where haematopoiesis occurs throughout adulthood1. Unique features of bone that contribute to a microenvironmental niche for stem cells might include the known high concentration of calcium ions at the HSC-enriched endosteal surface. Cells respond to extracellular ionic calcium concentrations through the seven-transmembrane-spanning calcium-sensing receptor (CaR), which we identified as being expressed on HSCs. Here we show that, through the CaR, the simple ionic mineral content of the niche may dictate the preferential localization of adult mammalian haematopoiesis in bone. Antenatal mice deficient in CaR had primitive haematopoietic cells in the circulation and spleen, whereas few were found in bone marrow. CaR-/- HSCs from fetal liver were normal in number, in proliferative and differentiative function, and in migration and homing to the bone marrow. Yet they were highly defective in localizing anatomically to the endosteal niche, behaviour that correlated with defective adhesion to the extracellular matrix protein, collagen I. CaR has a function in retaining HSCs in close physical proximity to the endosteal surface and the regulatory niche components associated with it. © 2006 Nature Publishing Group.

引用

页码：599 / 603

页数：4

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