Abstract
The interaction of hematopoietic stem and progenitor cells with their direct neighboring cells in the bone marrow (the so called hematopoietic niche) evolves as a key principle for understanding physiological and malignant hematopoiesis. Significant progress in this matter has recently been achieved making use of emerging high-throughput techniques that allow characterization of the bone marrow microenvironment at single cell resolution. This review aims to discuss these single cell findings in the light of other conventional niche studies that together define the current notion of the niche’s implication in (i) normal hematopoiesis, (ii) myeloid neoplasms and (iii) disease-driving pathways that can be exploited to establish novel therapeutic strategies in the future.
Highlights
The bone marrow (BM) microenvironment— referred to as BM niche—is the functional unit of multiple distinct cell types providing a balanced milieu for hematopoietic stem and progenitor cell (HSPC) populations to ensure well-regulated, physiological maturation along all blood lineages
While Tikhonova AN et al [4] single cell sequenced highly purified niche populations (Cdh5-Cre, leptin receptor (Lepr)-Cre, Col2.3-Cre lines crossed to a mouse strain expressing tdTomato under the control of a floxed transcriptional stop site), Baryawno N et al [5] selected an unbiased approach on lineage-depleted stromal niche cells
This is in line with recent reports demonstrating increased reactive oxygen species (ROS) in a cohort of patients with myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia [38]
Summary
The bone marrow (BM) microenvironment— referred to as BM niche—is the functional unit of multiple distinct cell types providing a balanced milieu for hematopoietic stem and progenitor cell (HSPC) populations to ensure well-regulated, physiological maturation along all blood lineages. For this review we prefer to apply a more global picture defining the BM niche as the collectivity of cells surrounding and fostering HSPC populations, forming a closely interwoven pro-hematopoietic network. The identification of CD45− stromal-associated cells with phenotypic and functional characteristics of B lymphoid and erythroid progenitors indicates that the general conception of the BM microenvironment is still incomplete [10]. This overall complex composition is a serious obstacle for studies to provide a full comprehensive analysis of the BM microenvironment in vivo
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