TY - JOUR TI - Identification of phenotypically, functionally, and anatomically distinct stromal niche populations in human bone marrow based on single-cell RNA sequencing AU - Li, Hongzhe AU - Bräunig, Sandro AU - Dhapolar, Parashar AU - Karlsson, Göran AU - Lang, Stefan AU - Scheding, Stefan A2 - Méndez-Ferrer, Simón A2 - Zaidi, Mone A2 - Strunk, Dirk A2 - Oostendorp, Robert AJ VL - 12 PY - 2023 DA - 2023/03/06 SP - e81656 C1 - eLife 2023;12:e81656 DO - 10.7554/eLife.81656 UR - https://doi.org/10.7554/eLife.81656 AB - Hematopoiesis is regulated by the bone marrow (BM) stroma. However, cellular identities and functions of the different BM stromal elements in humans remain poorly defined. Based on single-cell RNA sequencing (scRNAseq), we systematically characterized the human non-hematopoietic BM stromal compartment and we investigated stromal cell regulation principles based on the RNA velocity analysis using scVelo and studied the interactions between the human BM stromal cells and hematopoietic cells based on ligand-receptor (LR) expression using CellPhoneDB. scRNAseq led to the identification of six transcriptionally and functionally distinct stromal cell populations. Stromal cell differentiation hierarchy was recapitulated based on RNA velocity analysis and in vitro proliferation capacities and differentiation potentials. Potential key factors that might govern the transition from stem and progenitor cells to fate-committed cells were identified. In situ localization analysis demonstrated that different stromal cells were localized in different niches in the bone marrow. In silico cell-cell communication analysis further predicted that different stromal cell types might regulate hematopoiesis through distinct mechanisms. These findings provide the basis for a comprehensive understanding of the cellular complexity of the human BM microenvironment and the intricate stroma-hematopoiesis crosstalk mechanisms, thus refining our current view on human hematopoietic niche organization. KW - hematopoietic microenvironment KW - human bone marrow KW - stromal stem/progenitor cells KW - single-cell RNA sequencing KW - differentiation hierarchy KW - hematopoietic-stromal communication JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -