Cellular Niches for Hematopoietic Stem Cells and Lympho-Hematopoiesis in Bone Marrow During Homeostasis and Blood Cancers

Most types of blood cells, including immune cells are generated from hematopoietic stem cells (HSCs) within bone marrow in the adult. Most HSCs are in contact with and require the special microenvironment known as a niche for their maintenance. It has been thought that HSC niches comprise various types of support cells that provide critical signals, including cytokines and extracellular matrix for HSC regulation. However, among these cells, several lines of evidence have demonstrated that the population of bone marrow-specific mesenchymal stem cells, termed CXC chemokine ligand 12 (CXCL12)-abundant reticular (CAR) cells, which overlap strongly with leptin receptor-expressing (LepR(+)) cells, is the major cellular component of HSC niches. CAR/LepR(+) cells give rise to most adipocytes and osteoblasts in adult bone marrow and express much higher levels of HSC niche factors, including cytokines CXCL12 and stem cell factor (SCF), which are essential for HSC maintenance, and transcription factors Foxc1 and Ebf3, which are essential for the formation and maintenance of HSC niches than other types of cells. CAR/LepR(+) cells are present in human bone marrow, undergo fibrotic expansion, and have reduced expression of HSC niche factors in hematopoietic malignancies.