1. Biochemistry and Chemical Biology
  2. Developmental Biology

O-GlcNAc glycosylation orchestrates fate decision and niche function of bone marrow stromal progenitors

  1. Zengdi Zhang
  2. Zan Huang
  3. Mohamed Awad
  4. Mohammed Elsalanty
  5. James Cray
  6. Lauren E Ball
  7. Jason C Maynard
  8. Alma L Burlingame
  9. Hu Zeng
  10. Kim C Mansky
  11. Hai-Bin Ruan  Is a corresponding author
  1. University of Minnesota, United States
  2. Nanjing Agricultural University, China
  3. Western University of Health Sciences, United States
  4. The Ohio State University, United States
  5. University of South Carolina, United States
  6. University of California, San Francisco, United States
  7. Mayo Clinic, United States
https://doi.org/10.7554/eLife.85464
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Cite this article
  1. Zengdi Zhang
  2. Zan Huang
  3. Mohamed Awad
  4. Mohammed Elsalanty
  5. James Cray
  6. Lauren E Ball
  7. Jason C Maynard
  8. Alma L Burlingame
  9. Hu Zeng
  10. Kim C Mansky
  11. Hai-Bin Ruan
(2023)
O-GlcNAc glycosylation orchestrates fate decision and niche function of bone marrow stromal progenitors
eLife 12:e85464.
https://doi.org/10.7554/eLife.85464
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  3. Download .RIS

Abstract

In mammals, interactions between the bone marrow (BM) stroma and hematopoietic progenitors contribute to bone-BM homeostasis. Perinatal bone growth and ossification provide a microenvironment for the transition to definitive hematopoiesis; however, mechanisms and interactions orchestrating the development of skeletal and hematopoietic systems remain largely unknown. Here, we establish intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification as a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs). By modifying and activating RUNX2, O-GlcNAcylation promotes osteogenic differentiation of BMSCs and stromal IL-7 expression to support lymphopoiesis. In contrast, C/EBPβ-dependent marrow adipogenesis and expression of myelopoietic stem cell factor (SCF) is inhibited by O-GlcNAcylation. Ablating O-GlcNAc transferase (OGT) in BMSCs leads to impaired bone formation, increased marrow adiposity, as well as defective B-cell lymphopoiesis and myeloid overproduction in mice. Thus, the balance of osteogenic and adipogenic differentiation of BMSCs is determined by reciprocal O-GlcNAc regulation of transcription factors, which simultaneously shapes the hematopoietic niche.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting file. Supplemental tables have been provided for Mass spectrometry, primer sequences, and antibody list.

Article and author information

Author details

  1. Zengdi Zhang

    Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Zan Huang

    Laboratory of Gastrointestinal Microbiology, Nanjing Agricultural University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.

  3. Mohamed Awad

    Department of Medical Anatomical Sciences, Western University of Health Sciences, Pomona, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Mohammed Elsalanty

    Department of Medical Anatomical Sciences, Western University of Health Sciences, Pomona, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. James Cray

    Department of Biomedical Education and Anatomy, The Ohio State University, Columbus, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Lauren E Ball

    6Department of Cell and Molecular Pharmacology and Experimental Therapeutics, University of South Carolina, Charleston, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Jason C Maynard

    Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Alma L Burlingame

    Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  9. Hu Zeng

    Department of Internal Medicine, Mayo Clinic, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.

  10. Kim C Mansky

    Department of Developmental and Surgical Sciences, University of Minnesota, Minneapolis, United States
    Competing interests
    The authors declare that no competing interests exist.

  11. Hai-Bin Ruan

    Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, United States
    For correspondence
    hruan@umn.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3858-1272

Funding

National Natural Science Foundation of China (32170847)

  • Zan Huang

National Institutes of Health (R01 AI162678)

  • Hu Zeng

National Institutes of Health (R01 AI139420)

  • Hai-Bin Ruan

National Institutes of Health (R01 AI162791)

  • Hai-Bin Ruan

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

Reviewing Editor

  1. Yunlei Yang, Albert Einstein College of Medicine, United States

Ethics

Animal experimentation: All animal experiments were approved by the institutional animal care and use committee of the University of Minnesota (protocol # 2112-39682A).

Version history

  1. Received: December 8, 2022
  2. Preprint posted: December 21, 2022 (view preprint)
  3. Accepted: March 1, 2023
  4. Accepted Manuscript published: March 2, 2023 (version 1)
  5. Version of Record published: March 22, 2023 (version 2)

Copyright

© 2023, Zhang 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. Zengdi Zhang
  2. Zan Huang
  3. Mohamed Awad
  4. Mohammed Elsalanty
  5. James Cray
  6. Lauren E Ball
  7. Jason C Maynard
  8. Alma L Burlingame
  9. Hu Zeng
  10. Kim C Mansky
  11. Hai-Bin Ruan
(2023)
O-GlcNAc glycosylation orchestrates fate decision and niche function of bone marrow stromal progenitors
eLife 12:e85464.
https://doi.org/10.7554/eLife.85464

Share this article

https://doi.org/10.7554/eLife.85464

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