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Characterization of cells that form HSC niches

Hematopoietic stem cells (HSCs) are rare and cannot survive, expand or develop alone, so require specialized niches in the bone marrow for their maintenance and to help their differentiation into immune cells. In their Review, Tatsuki Sugiyama, Yoshiki Omatsu and Takashi Nagasawa detail how the most important niche involves contact of HSCs with CAR cells (CXCL12-abundant reticular cells; also called LepR⁺ cells). CAR cells are mesenchymal stem cells that express transcription factors (e.g. Foxc1 and Ebf3) and produce cytokines (e.g. CXCL12 and SCF) that are essential for the development of a wide variety of immune cell progenitor populations. CAR cells can also develop into adipocytes, osteoblasts and myofibroblasts. The authors also discuss the evidence showing contributions from other candidate cell types such as sinusoidal endothelial cells (ECs) and Nestin-expressing and/or NG2-expressing periarteriolar cells in supporting HSCs; osteoblasts, megakaryocytes and macrophages are other candidates. Further work is needed on lineage-specific niches and the role of niches in disease pathogenesis.