Abstract
The interactions of stem cells with their supportive microenvironmental niches are mediated by signaling networks that control the balance between cellular self-renewal and differentiation. In hematopoietic stem cells (HSCs), the bone marrow (BM) supports both of these processes within specialized niches, namely, osteoblastic and perivascular niche, which contain supportive cellular and non-cellular elements. This review discusses HSC niches and niche cell populations, focusing on the osteoblastic niche cells in three fractions: osteoblast-enriched ALCAM+Sca-1- and ALCAM-Sca-1-, and immature mesenchymal cell-enriched ALCAM-Sca-1+ cells. Gene expression profiling showed that the ALCAM-Sca-1+ fraction highly expressed cytokine-related genes whereas in the ALCAM+Sca-1- fraction the predominantly expressed genes were those related to cell adhesion. In addition, by using single-cell gene expression analysis, we identified an osteoblastic markerlow/- subpopulation in ALCAM+Sca-1- cells, which includes cells that express relatively high levels of pluripotent markers. Together, these findings indicate that multiple cell populations cooperatively support HSCs in the osteoblastic niche. Understanding the niche signals that regulate HSC maintenance and terminal differentiation could provide the basis for niche-based therapies that protect HSCs from various stresses and promote the ex vivo expansion of HSCs.
