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Single cell transcriptomics identifies a unique adipose lineage cell population that regulates bone marrow environment

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Cite this article as: eLife 2020;9:e54695 doi: 10.7554/eLife.54695

Abstract

Bone marrow mesenchymal lineage cells are a heterogeneous cell population involved in bone homeostasis and diseases such as osteoporosis. While it is long postulated that they originate from mesenchymal stem cells, the true identity of progenitors and their in vivo bifurcated differentiation routes into osteoblasts and adipocytes remain poorly understood. Here, by employing large scale single cell transcriptome analysis, we computationally defined mesenchymal progenitors at different stages and delineated their bi-lineage differentiation paths in young, adult and aging mice. One identified subpopulation is a unique cell type that expresses adipocyte markers but contains no lipid droplets. As non-proliferative precursors for adipocytes, they exist abundantly as pericytes and stromal cells that form a ubiquitous 3D network inside the marrow cavity. Functionally they play critical roles in maintaining marrow vasculature and suppressing bone formation. Therefore, we name them marrow adipogenic lineage precursors (MALPs) and conclude that they are a new component of marrow adipose tissue.

Data availability

Sequencing data have been deposited in GEO under accession code GSE145477

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Leilei Zhong

    Orthopaedic Surgery, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Lutian Yao

    Orthopaedic Surgery, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0652-2075
  3. Robert Joel Tower

    Orthopaedic Surgery, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Yulong Wei

    Orthopaedic Surgery, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Zhen Miao

    Biostatistics, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Jihwan Park

    Renal-Electrolyte and Hypertension Division of Department of Medicine, and Department of Genetics, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5728-912X
  7. Rojesh Shrestha

    Medicine and Genetics, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Luqiang Wang

    Orthopaedic Surgery, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Wei Yu

    Orthopaedic Surgery, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Nicholas Holdreith

    Pediatrics, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Xiaobin Huang

    Translational Research Program in Pediatric Orthopaedics, The Children's Hospital of Philadelphia, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Yejia Zhang

    Orthopaedic Surgery, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Wei Tong

    Pediatrics, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Yanqing Gong

    Division of Transnational Medicine and Human Genetics, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. Jaimo Ahn

    Orthopaedic Surgery, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  16. Katalin Susztak

    Renal-Electrolyte and Hypertension Division of Department of Medicine, and Department of Genetics, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  17. Nathanial Dyment

    Orthopaedic Surgery, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8708-112X
  18. Mingyao Li

    Biostatistics, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  19. Fanxin Long

    Translational Research Program in Pediatric Orthopaedics, The Children's Hospital of Philadelphia, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  20. Chider Chen

    Department of Oral and Maxillofacial Surgery/Pharmacology, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2899-1208
  21. Patrick Seale

    Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  22. Ling Qin

    Orthopaedic Surgery, University of Pennsylvania, Philadelphia, United States
    For correspondence
    qinling@pennmedicine.upenn.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2582-0078

Funding

National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR066098)

  • Ling Qin

National Institutes of Health (R03DE028026)

  • Chider Chen

National Institute of Diabetes and Digestive and Kidney Diseases (R01DK095803)

  • Ling Qin

Penn Center for Musculoskeletal Disorders (P30AR069619)

  • Ling Qin

National Institutes of Health (R21AR074570)

  • Ling Qin

American Heart Association (17GRNT33650029)

  • Yanqing Gong

National Institutes of Health (R01HL095675)

  • Wei Tong

National Institutes of Health (R01HL133828)

  • Wei Tong

Nihon University (F31HL139091)

  • Nicholas Holdreith

National Institute of Dental and Craniofacial Research (R00DE025915)

  • Chider Chen

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal work performed in this report was approved by the Institutional Animal Care and Use Committee (IACUC) at the University of Pennsylvania under Protocol 804112. University Laboratory Animal Resources (ULAR) of the University of Pennsylvania is responsible for the procurement, care, and use of all university-owned animals as approved by IACUC. Animal facilities in the University of Pennsylvania meet federal, state, and local guidelines for laboratory animal care and are accredited by the Association for the Assessment and Accreditation of Laboratory Animal Care International.

Reviewing Editor

  1. J Gage Crump, Keck School of Medicine of University of Southern California, United States

Publication history

  1. Received: December 23, 2019
  2. Accepted: April 11, 2020
  3. Accepted Manuscript published: April 14, 2020 (version 1)
  4. Version of Record published: May 13, 2020 (version 2)

Copyright

© 2020, Zhong 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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