Single cell analysis of Idh mutant growth plates identifies cell populations responsible for longitudinal bone growth and enchondroma formation
Abstract Enchondromas are a common tumor in bone that can occur as multiple lesions in enchondromatosis, which is associated with deformity of the affected bone. These lesions harbor somatic mutations in IDH and driving expression of a mutant Idh1 in Col2 expressing cells in mice causes an enchondro...
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Nature Portfolio
2024-10-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-76539-y |
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| author | Vijitha Puviindran Eijiro Shimada Zeyu Huang Xinyi Ma Ga I. Ban Yu Xiang Hongyuan Zhang Jianhong Ou Xiaolin Wei Makoto Nakagawa John Martin Yarui Diao Benjamin A. Alman |
| author_facet | Vijitha Puviindran Eijiro Shimada Zeyu Huang Xinyi Ma Ga I. Ban Yu Xiang Hongyuan Zhang Jianhong Ou Xiaolin Wei Makoto Nakagawa John Martin Yarui Diao Benjamin A. Alman |
| author_sort | Vijitha Puviindran |
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| description | Abstract Enchondromas are a common tumor in bone that can occur as multiple lesions in enchondromatosis, which is associated with deformity of the affected bone. These lesions harbor somatic mutations in IDH and driving expression of a mutant Idh1 in Col2 expressing cells in mice causes an enchondromatosis phenotype. Here we compared growth plates from E18.5 mice expressing a mutant Idh1 with control littermates using single cell RNA sequencing. Data from Col2 expressing cells were analysed using UMAP and RNA pseudo-time analyses. A unique cluster of cells was identified in the mutant growth plates that expressed genes known to be upregulated in enchondromas. There was also a cluster of cells that was underrepresented in the mutant growth plates that expressed genes known to be important in longitudinal bone growth. Immunofluorescence showed that the genes from the unique cluster identified in the mutant growth plates were expressed in multiple growth plate anatomic zones, and pseudo-time analysis also suggested these cells could arise from multiple growth plate chondrocyte subpopulations. This data supports the notion that a subpopulation of chondrocytes become enchondromas at the expense of contributing to longitudinal growth. |
| format | Article |
| id | doaj-art-8e81d6bdfd804dc8a1418820475a7f9d |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-8e81d6bdfd804dc8a1418820475a7f9d2025-08-20T02:18:28ZengNature PortfolioScientific Reports2045-23222024-10-0114111210.1038/s41598-024-76539-ySingle cell analysis of Idh mutant growth plates identifies cell populations responsible for longitudinal bone growth and enchondroma formationVijitha Puviindran0Eijiro Shimada1Zeyu Huang2Xinyi Ma3Ga I. Ban4Yu Xiang5Hongyuan Zhang6Jianhong Ou7Xiaolin Wei8Makoto Nakagawa9John Martin10Yarui Diao11Benjamin A. Alman12Department of Orthopedic Surgery, Duke University School of MedicineDepartment of Orthopedic Surgery, Duke University School of MedicineDepartment of Orthopedic Surgery, Duke University School of MedicineDepartment of Orthopedic Surgery, Duke University School of MedicineDepartment of Orthopedic Surgery, Duke University School of MedicineDepartment of Cell Biology, Duke University School of MedicineDepartment of Orthopedic Surgery, Duke University School of MedicineRegeneration Center, Duke University School of MedicineDepartment of Cell Biology, Duke University School of MedicineDepartment of Orthopedic Surgery, Duke University School of MedicineDepartment of Orthopedic Surgery, Duke University School of MedicineDepartment of Orthopedic Surgery, Duke University School of MedicineDepartment of Orthopedic Surgery, Duke University School of MedicineAbstract Enchondromas are a common tumor in bone that can occur as multiple lesions in enchondromatosis, which is associated with deformity of the affected bone. These lesions harbor somatic mutations in IDH and driving expression of a mutant Idh1 in Col2 expressing cells in mice causes an enchondromatosis phenotype. Here we compared growth plates from E18.5 mice expressing a mutant Idh1 with control littermates using single cell RNA sequencing. Data from Col2 expressing cells were analysed using UMAP and RNA pseudo-time analyses. A unique cluster of cells was identified in the mutant growth plates that expressed genes known to be upregulated in enchondromas. There was also a cluster of cells that was underrepresented in the mutant growth plates that expressed genes known to be important in longitudinal bone growth. Immunofluorescence showed that the genes from the unique cluster identified in the mutant growth plates were expressed in multiple growth plate anatomic zones, and pseudo-time analysis also suggested these cells could arise from multiple growth plate chondrocyte subpopulations. This data supports the notion that a subpopulation of chondrocytes become enchondromas at the expense of contributing to longitudinal growth.https://doi.org/10.1038/s41598-024-76539-y |
| spellingShingle | Vijitha Puviindran Eijiro Shimada Zeyu Huang Xinyi Ma Ga I. Ban Yu Xiang Hongyuan Zhang Jianhong Ou Xiaolin Wei Makoto Nakagawa John Martin Yarui Diao Benjamin A. Alman Single cell analysis of Idh mutant growth plates identifies cell populations responsible for longitudinal bone growth and enchondroma formation Scientific Reports |
| title | Single cell analysis of Idh mutant growth plates identifies cell populations responsible for longitudinal bone growth and enchondroma formation |
| title_full | Single cell analysis of Idh mutant growth plates identifies cell populations responsible for longitudinal bone growth and enchondroma formation |
| title_fullStr | Single cell analysis of Idh mutant growth plates identifies cell populations responsible for longitudinal bone growth and enchondroma formation |
| title_full_unstemmed | Single cell analysis of Idh mutant growth plates identifies cell populations responsible for longitudinal bone growth and enchondroma formation |
| title_short | Single cell analysis of Idh mutant growth plates identifies cell populations responsible for longitudinal bone growth and enchondroma formation |
| title_sort | single cell analysis of idh mutant growth plates identifies cell populations responsible for longitudinal bone growth and enchondroma formation |
| url | https://doi.org/10.1038/s41598-024-76539-y |
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