Abstract
Self-renewal and multidirectional differentiation of hematopoietic stem cells (HSCs) are strictly regulated by numerous cellular components and cytokines in the bone marrow (BM) microenvironment. Several cell types that regulate HSC niche have been identified, including both non-hematopoietic cells and HSC-derived cells. Specific changes in the niche composition can result in hematological malignancies. Furthermore, processes such as homing, proliferation, and differentiation of HSCs are strongly controlled by the BM niche and have been reported to be related to the success of hematopoietic stem cell transplantation (HSCT). Single-cell sequencing and in vivo imaging are powerful techniques to study BM microenvironment in hematological malignancies and after HSCT. In this review, we discuss how different components of the BM niche, particularly non-hematopoietic and hematopoietic cells, regulate normal hematopoiesis, and changes in the BM niche in leukemia and after HSCT. We believe that this comprehensive review will provide clues for further research on improving HSCT efficiency and exploring potential therapeutic targets for leukemia.
Highlights
The concept of hematopoietic stem cell (HSC) niche was first proposed by Schofield (1978), who proposed that a physical niche of stem cells exists in the bone marrow (BM)
Nestin+ Mesenchymal stem cells (MSCs) are in close contact with adrenergic nerves (Mendez-Ferrer et al, 2010), and the removal of sympathetic nerve fibers leads to reduced Nestin+ MSC cells, which in turn promotes HSC expansion and myeloproliferative neoplasia (MPN) development (Baryawno and Scadden, 2014)
Kong (Wang et al, 2016) found that as compared with good graft function (GGF) and healthy donors, the percentage of T-helper cell 1 (Th1) and T killer cell 1 (Tc1) cells producing IFN-γ increased in patients with poor graft function (PGF) after allo hematopoietic stem cell transplantation (HSCT), whereas the percentage of Th2 and Tc2 cells that produce IL-4 decreased, resulting in an increased proportion of Th1/Th2 and Tc1/Tc2
Summary
The concept of hematopoietic stem cell (HSC) niche was first proposed by Schofield (1978), who proposed that a physical niche of stem cells exists in the bone marrow (BM). The niche consists of a variety of cells that make the microenvironment for the maintenance of stem cells. The proliferation of normal hematopoietic stem and progenitor cells (HSPCs) is inhibited and most HSCs enter into the quiescent stage, whereas hematopoietic progenitor cells (HPCs) overproliferate and are gradually exhausted (Hu et al, 2009). The inhibitory effect on normal hematopoiesis in leukemia is reversible (Cheng et al, 2015), implying that niche factors govern the malignant characteristics. Hematopoietic stem cell transplantation (HSCT) is one of the most effective methods for treating hematologic malignancy. A recent study based on singlecell sequencing reported that transplanted HSCs decreased gradually within 1 week in myeloablated recipients, and the potential to differentiate into myeloid and erythroid lineages enhanced in some of the remaining HSCs (Dong et al, 2020). An in-depth study of changes in the BM microenvironment before and after HSCT is required to explore potential therapeutic targets for leukemia
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