Cellular niches for hematopoietic stem cells in bone marrow under normal and malignant conditions

Throughout adult life, most lineages of blood cells, including immune cells, are generated from hematopoietic stem cells (HSCs) in the bone marrow. HSCs are thought to require special microenvironments, termed niches, for their maintenance in the bone marrow; however, the identity of the HSC cellular niche has been a subject of long-standing debate. Although diverse candidates have been proposed so far, accumulated studies demonstrate that the bone marrow-specific population of fibroblastic reticular cells with long processes, termed CXC chemokine ligand 12-abundant reticular cells (which overlap strongly with leptin receptor-expressing cells), termed CAR/LepR⁺ cells, are the pivotal cellular component of niches for HSCs and lymphoid progenitors. Sinusoidal endothelial cells (ECs) are also important for hematopoietic homeostasis and regeneration. Hematopoiesis is altered dynamically by various stimuli such as inflammation, infection, and leukemia, all of which affect cellular niches and alter their function. Therefore, it is important to consider situations in which stimuli affect HSCs, either via direct interaction or indirectly via the hematopoietic niches. In this review, the dynamics of cellular niches in the steady state and disease are described, with a focus on CAR/LepR⁺ cells and ECs.