Identification of phenotypically, functionally, and anatomically distinct stromal niche populations in human bone marrow based on single-cell RNA sequencing
- Lund University, Sweden
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 (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.
Data availability
The scRNA-seq matrix data generated in this study have been deposited in the GEO database (GSE190965).
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Transcriptomic profiling of human bone marrow non-hematopoietic cellsNCBI Gene Expression Omnibus, GSE190965.
Article and author information
Author details
Funding
Swedish Cancer Foundation (20-1163PjF 01H)
- Stefan Scheding
Swedish Childhood Cancer Foundation (PR2018-0078)
- Stefan Scheding
Swedish Childhood Cancer Foundation (PR2021-0065)
- Stefan Scheding
Swedish Bloodcancer Association (N.A.)
- Stefan Scheding
Swedish Research Council (N.A.)
- Stefan Scheding
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: Human bone marrow (BM) cells were collected at the Hematology Department, Skåne University Hospital Lund, Sweden, from consenting healthy donors. The use of human samples was approved by the Regional Ethics Review Board in Lund, Sweden.
Copyright
© 2023, Li et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Identification of phenotypically, functionally, and anatomically distinct stromal niche populations in human bone marrow based on single-cell RNA sequencing
eLife 12:e81656.
https://doi.org/10.7554/eLife.81656
