The role of chemokine CXCL12 and CXCL12 abundant reticular cells in formation of microenvironmental niches for hematopoiesis

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The special microenvironments known as niches, where hematopoietic stem cells (HSCs) and hematopoietic cells reside are thought to supply the requisite factors and play an essential role in their maintenance and regulation. It has been reported previously that HSCs reside near bone surfaces and/or near the vasculature and that a population of osteoblasts and/or endothelial cells might function as niches for HSCs; however, their functions and molecular regulatory mechanism remain unclear. The chemokine CXCL12 and its receptor CXCR4 are essential for colonization of bone marrow by HSCs during ontogeny and development of B cells. In this project, we have shown that the induced deletion of CXCR4 in adult mice results in severe reduction of HSC numbers. In addition, most HSCs were found in contact with the processes of a small population of non-hematopoietic cells expressing high amounts of CXCL12, termed CXCL12-abundant reticular (CAR) cells, some of which surrounded sinusoidal endothelial cells or were located near the endosteum. CAR cells are scattered throughout bone marrow and have long processes. These findings indicate that CXCL12-CXCR4 signaling plays an essential role in maintaining the HSC pool, and suggest that CAR cells are a key component of HSC niches in bone marrow.