O-GlcNAc glycosylation orchestrates fate decision and niche function of bone marrow stromal progenitors
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 devel...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-03-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/85464 |
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| author | Zengdi Zhang Zan Huang Mohamed Awad Mohammed Elsalanty James Cray Lauren E Ball Jason C Maynard Alma L Burlingame Hu Zeng Kim C Mansky Hai-Bin Ruan |
| author_facet | Zengdi Zhang Zan Huang Mohamed Awad Mohammed Elsalanty James Cray Lauren E Ball Jason C Maynard Alma L Burlingame Hu Zeng Kim C Mansky Hai-Bin Ruan |
| author_sort | Zengdi Zhang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T22:21:55Z |
| format | Article |
| id | doaj.art-9f3565164f5a4c418d666d711bac7fd1 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-09T22:21:55Z |
| publishDate | 2023-03-01 |
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| series | eLife |
| spelling | doaj.art-9f3565164f5a4c418d666d711bac7fd12023-03-22T14:54:43ZengeLife Sciences Publications LtdeLife2050-084X2023-03-011210.7554/eLife.85464O-GlcNAc glycosylation orchestrates fate decision and niche function of bone marrow stromal progenitorsZengdi Zhang0Zan Huang1Mohamed Awad2Mohammed Elsalanty3James Cray4Lauren E Ball5Jason C Maynard6Alma L Burlingame7Hu Zeng8Kim C Mansky9Hai-Bin Ruan10https://orcid.org/0000-0002-3858-1272Department of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, United StatesDepartment of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, United States; Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China; National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing, ChinaDepartment of Medical Anatomical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, United StatesDepartment of Medical Anatomical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, United StatesDepartment of Biomedical Education and Anatomy, The Ohio State University College of Medicine, and Division of Biosciences, The Ohio State University College of Dentistry, Columbus, United StatesDepartment of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, Charleston, United StatesDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United StatesDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United StatesDivision of Rheumatology, Department of Internal Medicine, Mayo Clinic, Rochester, United States; Department of Immunology, Mayo Clinic, Rochester, United StatesDepartment of Developmental and Surgical Sciences, School of Dentistry, University of Minnesota, Minneapolis, United StatesDepartment of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, United States; Center for Immunology, University of Minnesota Medical School, Minneapolis, United StatesIn 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.https://elifesciences.org/articles/85464bonebone marrowhematopoiesis |
| spellingShingle | Zengdi Zhang Zan Huang Mohamed Awad Mohammed Elsalanty James Cray Lauren E Ball Jason C Maynard Alma L Burlingame Hu Zeng Kim C Mansky Hai-Bin Ruan O-GlcNAc glycosylation orchestrates fate decision and niche function of bone marrow stromal progenitors eLife bone bone marrow hematopoiesis |
| title | O-GlcNAc glycosylation orchestrates fate decision and niche function of bone marrow stromal progenitors |
| title_full | O-GlcNAc glycosylation orchestrates fate decision and niche function of bone marrow stromal progenitors |
| title_fullStr | O-GlcNAc glycosylation orchestrates fate decision and niche function of bone marrow stromal progenitors |
| title_full_unstemmed | O-GlcNAc glycosylation orchestrates fate decision and niche function of bone marrow stromal progenitors |
| title_short | O-GlcNAc glycosylation orchestrates fate decision and niche function of bone marrow stromal progenitors |
| title_sort | o glcnac glycosylation orchestrates fate decision and niche function of bone marrow stromal progenitors |
| topic | bone bone marrow hematopoiesis |
| url | https://elifesciences.org/articles/85464 |
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