1. Stem Cells and Regenerative Medicine

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

  1. Hongzhe Li
  2. Sandro Bräunig
  3. Parashar Dhapolar
  4. Göran Karlsson
  5. Stefan Lang
  6. Stefan Scheding  Is a corresponding author
  1. Lund University, Sweden
https://doi.org/10.7554/eLife.81656
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  1. Hongzhe Li
  2. Sandro Bräunig
  3. Parashar Dhapolar
  4. Göran Karlsson
  5. Stefan Lang
  6. Stefan Scheding
(2023)
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
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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).

The following data sets were generated

Article and author information

Author details

  1. Hongzhe Li

    Division of Molecular Hematology and Stem Cell Center, Lund University, Lund, Sweden
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7788-878X

  2. Sandro Bräunig

    Division of Molecular Hematology and Stem Cell Center, Lund University, Lund, Sweden
    Competing interests
    The authors declare that no competing interests exist.

  3. Parashar Dhapolar

    Division of Molecular Hematology and Stem Cell Center, Lund University, Lund, Sweden
    Competing interests
    The authors declare that no competing interests exist.

  4. Göran Karlsson

    Division of Molecular Hematology and Stem Cell Center, Lund University, Lund, Sweden
    Competing interests
    The authors declare that no competing interests exist.

  5. Stefan Lang

    Division of Molecular Hematology and Stem Cell Center, Lund University, Lund, Sweden
    Competing interests
    The authors declare that no competing interests exist.

  6. Stefan Scheding

    Division of Molecular Hematology and Stem Cell Center, Lund University, Lund, Sweden
    For correspondence
    stefan.scheding@med.lu.se
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8005-9568

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.

Reviewing Editor

  1. Simón Méndez-Ferrer, University of Cambridge, United Kingdom

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.

Version history

  1. Preprint posted: January 27, 2022 (view preprint)
  2. Received: July 6, 2022
  3. Accepted: March 2, 2023
  4. Accepted Manuscript published: March 6, 2023 (version 1)
  5. Accepted Manuscript updated: March 7, 2023 (version 2)
  6. Version of Record published: April 12, 2023 (version 3)

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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  1. Hongzhe Li
  2. Sandro Bräunig
  3. Parashar Dhapolar
  4. Göran Karlsson
  5. Stefan Lang
  6. Stefan Scheding
(2023)
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

Share this article

https://doi.org/10.7554/eLife.81656

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