Hypertrophic chondrocytes serve as a reservoir for marrow-associated skeletal stem and progenitor cells, osteoblasts, and adipocytes during skeletal development
Hypertrophic chondrocytes give rise to osteoblasts during skeletal development; however, the process by which these non-mitotic cells make this transition is not well understood. Prior studies have also suggested that skeletal stem and progenitor cells (SSPCs) localize to the surrounding periosteum...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-02-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/76932 |
| _version_ | 1828375151546204160 |
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| author | Jason T Long Abigail Leinroth Yihan Liao Yinshi Ren Anthony J Mirando Tuyet Nguyen Wendi Guo Deepika Sharma Douglas Rouse Colleen Wu Kathryn Song Eng Cheah Courtney M Karner Matthew J Hilton |
| author_facet | Jason T Long Abigail Leinroth Yihan Liao Yinshi Ren Anthony J Mirando Tuyet Nguyen Wendi Guo Deepika Sharma Douglas Rouse Colleen Wu Kathryn Song Eng Cheah Courtney M Karner Matthew J Hilton |
| author_sort | Jason T Long |
| collection | DOAJ |
| description | Hypertrophic chondrocytes give rise to osteoblasts during skeletal development; however, the process by which these non-mitotic cells make this transition is not well understood. Prior studies have also suggested that skeletal stem and progenitor cells (SSPCs) localize to the surrounding periosteum and serve as a major source of marrow-associated SSPCs, osteoblasts, osteocytes, and adipocytes during skeletal development. To further understand the cell transition process by which hypertrophic chondrocytes contribute to osteoblasts or other marrow associated cells, we utilized inducible and constitutive hypertrophic chondrocyte lineage tracing and reporter mouse models (Col10a1CreERT2; Rosa26fs-tdTomato and Col10a1Cre; Rosa26fs-tdTomato) in combination with a PDGFRaH2B-GFP transgenic line, single-cell RNA-sequencing, bulk RNA-sequencing, immunofluorescence staining, and cell transplantation assays. Our data demonstrate that hypertrophic chondrocytes undergo a process of dedifferentiation to generate marrow-associated SSPCs that serve as a primary source of osteoblasts during skeletal development. These hypertrophic chondrocyte-derived SSPCs commit to a CXCL12-abundant reticular (CAR) cell phenotype during skeletal development and demonstrate unique abilities to recruit vasculature and promote bone marrow establishment, while also contributing to the adipogenic lineage. |
| first_indexed | 2024-04-14T07:43:46Z |
| format | Article |
| id | doaj.art-e5000bdddb6c48f5925edceea43da35c |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:43:46Z |
| publishDate | 2022-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-e5000bdddb6c48f5925edceea43da35c2022-12-22T02:05:25ZengeLife Sciences Publications LtdeLife2050-084X2022-02-011110.7554/eLife.76932Hypertrophic chondrocytes serve as a reservoir for marrow-associated skeletal stem and progenitor cells, osteoblasts, and adipocytes during skeletal developmentJason T Long0https://orcid.org/0000-0002-6006-0932Abigail Leinroth1Yihan Liao2Yinshi Ren3Anthony J Mirando4Tuyet Nguyen5https://orcid.org/0000-0002-8769-9955Wendi Guo6Deepika Sharma7Douglas Rouse8Colleen Wu9Kathryn Song Eng Cheah10https://orcid.org/0000-0003-0802-8799Courtney M Karner11Matthew J Hilton12https://orcid.org/0000-0003-3165-267XDepartment of Cell Biology, Duke University School of Medicine, Durham, United States; Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, United StatesDepartment of Cell Biology, Duke University School of Medicine, Durham, United States; Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, United StatesDepartment of Orthopaedic Surgery, Duke University School of Medicine, Durham, United States; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United StatesDepartment of Orthopaedic Surgery, Duke University School of Medicine, Durham, United StatesDepartment of Orthopaedic Surgery, Duke University School of Medicine, Durham, United StatesProgram of Developmental and Stem Cell Biology, Duke University School of Medicine, Durham, United StatesDepartment of Orthopaedic Surgery, Duke University School of Medicine, Durham, United States; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United StatesDepartment of Orthopaedic Surgery, Duke University School of Medicine, Durham, United StatesDivision of Laboratory Animal Resources, Duke University School of Medicine, Durham, United StatesDepartment of Cell Biology, Duke University School of Medicine, Durham, United States; Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, United States; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United StatesSchool of Biomedical Sciences, University of Hong Kong, Hong Kong, Hong KongDepartment of Cell Biology, Duke University School of Medicine, Durham, United States; Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, United StatesDepartment of Cell Biology, Duke University School of Medicine, Durham, United States; Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, United StatesHypertrophic chondrocytes give rise to osteoblasts during skeletal development; however, the process by which these non-mitotic cells make this transition is not well understood. Prior studies have also suggested that skeletal stem and progenitor cells (SSPCs) localize to the surrounding periosteum and serve as a major source of marrow-associated SSPCs, osteoblasts, osteocytes, and adipocytes during skeletal development. To further understand the cell transition process by which hypertrophic chondrocytes contribute to osteoblasts or other marrow associated cells, we utilized inducible and constitutive hypertrophic chondrocyte lineage tracing and reporter mouse models (Col10a1CreERT2; Rosa26fs-tdTomato and Col10a1Cre; Rosa26fs-tdTomato) in combination with a PDGFRaH2B-GFP transgenic line, single-cell RNA-sequencing, bulk RNA-sequencing, immunofluorescence staining, and cell transplantation assays. Our data demonstrate that hypertrophic chondrocytes undergo a process of dedifferentiation to generate marrow-associated SSPCs that serve as a primary source of osteoblasts during skeletal development. These hypertrophic chondrocyte-derived SSPCs commit to a CXCL12-abundant reticular (CAR) cell phenotype during skeletal development and demonstrate unique abilities to recruit vasculature and promote bone marrow establishment, while also contributing to the adipogenic lineage.https://elifesciences.org/articles/76932hypertrophic chondrocytesosteoblastsadipocytesbone marrowprogenitor cellsskeletal stem |
| spellingShingle | Jason T Long Abigail Leinroth Yihan Liao Yinshi Ren Anthony J Mirando Tuyet Nguyen Wendi Guo Deepika Sharma Douglas Rouse Colleen Wu Kathryn Song Eng Cheah Courtney M Karner Matthew J Hilton Hypertrophic chondrocytes serve as a reservoir for marrow-associated skeletal stem and progenitor cells, osteoblasts, and adipocytes during skeletal development eLife hypertrophic chondrocytes osteoblasts adipocytes bone marrow progenitor cells skeletal stem |
| title | Hypertrophic chondrocytes serve as a reservoir for marrow-associated skeletal stem and progenitor cells, osteoblasts, and adipocytes during skeletal development |
| title_full | Hypertrophic chondrocytes serve as a reservoir for marrow-associated skeletal stem and progenitor cells, osteoblasts, and adipocytes during skeletal development |
| title_fullStr | Hypertrophic chondrocytes serve as a reservoir for marrow-associated skeletal stem and progenitor cells, osteoblasts, and adipocytes during skeletal development |
| title_full_unstemmed | Hypertrophic chondrocytes serve as a reservoir for marrow-associated skeletal stem and progenitor cells, osteoblasts, and adipocytes during skeletal development |
| title_short | Hypertrophic chondrocytes serve as a reservoir for marrow-associated skeletal stem and progenitor cells, osteoblasts, and adipocytes during skeletal development |
| title_sort | hypertrophic chondrocytes serve as a reservoir for marrow associated skeletal stem and progenitor cells osteoblasts and adipocytes during skeletal development |
| topic | hypertrophic chondrocytes osteoblasts adipocytes bone marrow progenitor cells skeletal stem |
| url | https://elifesciences.org/articles/76932 |
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