Single-cell RNA sequencing identifies phenotypically, functionally, and anatomically distinct stromal niche populations in human bone marrow

Abstract

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, we systematically characterized the BM stromal compartment which led to the identification of six transcriptionally and functionally distinct stromal cell populations. Stromal cell differentiation hierarchy was recapitulated based on RNA velocity analysis, in vitro proliferation capacities and differentiation potentials. Potential key factors that govern the transition from stem and progenitor cells to fate-committed cells were identified. Cell-cell communication and in situ localization analysis demonstrated distinct hematopoietic stromal cell niches in specific BM locations, which used either the CXCL12 or SPP1 axis as the major hematopoiesis-regulating mechanism. 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 hematopoietic niche organization.

Stromal bone marrow fibroblasts and mesenchymal stem cells support acute myeloid leukaemia cells and promote therapy resistance

“…Similarly, Buechler et al (2021) illustrated the compartmentalisation of the murine fibroblast lineage into universal, specialised and activated subtypes, whereby a universal/common ancestor fibroblast population gives rise to tissue-specific specialised subtypes (steady state) that may acquire an activated phenotype during disease/infection. Based on these studies, scRNA-seq of human bone marrow stroma (CD45 low/À CD235a À CD271 + ) identified six stromal cell types across nine clusters, which included pre-fibroblasts and multipotent stromal stem cells (Li et al, 2022).…”