Fig. 4
From: Role of reactive oxygen species in myelodysplastic syndromes
a Cellular and molecular components of the HSC niche. The activity of HSC is regulated by various nonhematopoietic and hematopoietic cell types and niche regulatory factors. The target map shows how BM niche cells are indirectly or directly implicated in the regulation of HSCs through the synthesis of niche factors in the form of cell-bounding or secretory molecules. The color of radial spokes represents the affected HSC activity. Molecules with asterisks stand for involvement in BM regeneration after ablation. The bold molecules indicate molecules for which functional data were obtained via cell-specific genetic evidence. b The adult bone marrow HSC niche in homeostasis. Multiple cell types and niche regulatory factors are implicated in the regulation of HSC activity in a direct or indirect manner. Vasculature and associated stromal cells, including periarteriolar Nes-GFPhigh cells, NG2+ cells, and MYH11+ cells, as well as perisinusoidal Nes-GFPlow cells, CAR cells, and LEPR+ cells, are the essential regulators for HSC maintenance. The sympathetic nervous system nerves are involved in the mobilization of HSC, adipocytes perhaps negatively impact HSC maintenance, and nonmyelinating Schwann cells may lead to HSC quiescence. Osteoblasts not only take part in HSC regulation but also may play a prominent role in lymphoid progenitor regulation. Macrophages, neutrophils, Treg cells, megakaryocytes, and other hematopoietic cells are the progeny that differentiate from HSC. In addition, platelet-biased Vwf-GFP+ HSCs are distributed in and regulated by separate BM niches containing megakaryocytes, while myeloid-biased Vwf-GFP– HSCs are localized in and regulated by separate BM niches containing arterioles. c The relationship between ROS levels and HSCs destiny. Maintenance of low ROS levels is associated with hypoxic conditions and some regulators, such as HIF1, COX2, PGE2, CXCR4, and CXCL12. Raised ROS could drive HSCs out of the quiescent state and differentiation into short-term repopulating cells, and further differentiation into myeloid cells (e.g., erythrocytes, leukocytes, neutrophils, basophils, eosinophils, monocytes, lymphocytes, and platelets). However, excessive ROS levels can prompt the exhaustion of HSCs and then apoptosis/ferroptosis