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eLife
03 06, 2023;12

Identification of phenotypically, functionally, and anatomically distinct stromal niche populations in human bone marrow based on single-cell RNA sequencing.

Hongzhe Li, Sandro Bräunig, Parashar Dhapolar, Göran Karlsson, Stefan Lang, Stefan Scheding
Author Information
  1. Hongzhe Li: Division of Molecular Hematology and Stem Cell Center, Lund University, Lund, Sweden. ORCID
  2. Sandro Bräunig: Division of Molecular Hematology and Stem Cell Center, Lund University, Lund, Sweden. ORCID
  3. Parashar Dhapolar: Division of Molecular Hematology and Stem Cell Center, Lund University, Lund, Sweden.
  4. Göran Karlsson: Division of Molecular Hematology and Stem Cell Center, Lund University, Lund, Sweden.
  5. Stefan Lang: Division of Molecular Hematology and Stem Cell Center, Lund University, Lund, Sweden.
  6. Stefan Scheding: Division of Molecular Hematology and Stem Cell Center, Lund University, Lund, Sweden. ORCID
PMID: 36876630 DOI: 10.7554/eLife.81656

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.

Keywords

differentiation hierarchy hematopoietic microenvironment hematopoietic-stromal communication human human bone marrow regenerative medicine single-cell RNA sequencing stem cells stromal stem/progenitor cells

Associated Data

GEO | GSE190965

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Grants

  1. 20-1163PjF 01H/Swedish Cancer Foundation
  2. PR2018-0078/Swedish Childhood Cancer Foundation
  3. PR2021-0065/Swedish Childhood Cancer Foundation

MeSH Term

Humans
Bone Marrow
Hematopoietic Stem Cells
Stem Cell Niche
Bone Marrow Cells
Hematopoiesis
Sequence Analysis, RNA
RNA

Chemicals

RNA
Journal Article Research Support, Non-U.S. Gov't

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