Spatiotemporal Characterization of Human Early Intervertebral Disc Formation at Single‐Cell Resolution
Abstract The intervertebral disc (IVD) acts as a fibrocartilaginous joint to anchor adjacent vertebrae. Although several studies have demonstrated the cellular heterogeneity of adult mature IVDs, a single‐cell transcriptomic atlas mapping early IVD formation is still lacking. Here, the authors gener...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-05-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202206296 |
| _version_ | 1827946003274137600 |
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| author | Taifeng Zhou Yu Chen Zhiheng Liao Long Zhang Deying Su Zhuling Li Xiaoming Yang Xiaona Ke Hengyu Liu Yuyu Chen Ricong Weng Huimin Shen Caixia Xu Yong Wan Ren Xu Peiqiang Su |
| author_facet | Taifeng Zhou Yu Chen Zhiheng Liao Long Zhang Deying Su Zhuling Li Xiaoming Yang Xiaona Ke Hengyu Liu Yuyu Chen Ricong Weng Huimin Shen Caixia Xu Yong Wan Ren Xu Peiqiang Su |
| author_sort | Taifeng Zhou |
| collection | DOAJ |
| description | Abstract The intervertebral disc (IVD) acts as a fibrocartilaginous joint to anchor adjacent vertebrae. Although several studies have demonstrated the cellular heterogeneity of adult mature IVDs, a single‐cell transcriptomic atlas mapping early IVD formation is still lacking. Here, the authors generate a spatiotemporal and single cell‐based transcriptomic atlas of human IVD formation at the embryonic stage and a comparative mouse transcript landscape. They identify two novel human notochord (NC)/nucleus pulposus (NP) clusters, SRY‐box transcription factor 10 (SOX10)+ and cathepsin K (CTSK)+, that are distributed in the early and late stages of IVD formation and they are validated by lineage tracing experiments in mice. Matrisome NC/NP clusters, T‐box transcription factor T (TBXT)+ and CTSK+, are responsible for the extracellular matrix homeostasis. The IVD atlas suggests that a subcluster of the vertebral chondrocyte subcluster might give rise to an inner annulus fibrosus of chondrogenic origin, while the fibroblastic outer annulus fibrosus preferentially expresseds transgelin and fibromodulin . Through analyzing intercellular crosstalk, the authors further find that notochordal secreted phosphoprotein 1 (SPP1) is a novel cue in the IVD microenvironment, and it is associated with IVD development and degeneration. In conclusion, the single‐cell transcriptomic atlas will be leveraged to develop preventative and regenerative strategies for IVD degeneration. |
| first_indexed | 2024-03-13T10:51:27Z |
| format | Article |
| id | doaj.art-9b4d04ddba6b4ada80f1a48ca76af2cf |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-13T10:51:27Z |
| publishDate | 2023-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-9b4d04ddba6b4ada80f1a48ca76af2cf2023-05-17T13:02:05ZengWileyAdvanced Science2198-38442023-05-011014n/an/a10.1002/advs.202206296Spatiotemporal Characterization of Human Early Intervertebral Disc Formation at Single‐Cell ResolutionTaifeng Zhou0Yu Chen1Zhiheng Liao2Long Zhang3Deying Su4Zhuling Li5Xiaoming Yang6Xiaona Ke7Hengyu Liu8Yuyu Chen9Ricong Weng10Huimin Shen11Caixia Xu12Yong Wan13Ren Xu14Peiqiang Su15Department of Spine Surgery Guangdong Provincial Key Laboratory of Orthopedics and Traumatology The First Affiliated Hospital of Sun Yat‐sen University Guangzhou 510080 ChinaState Key Laboratory of Cellular Stress Biology Fujian Provincial Key Laboratory of Organ and Tissue Regeneration School of Medicine Faculty of Medicine and Life Sciences Xiamen University Xiamen 361102 ChinaDepartment of Spine Surgery Guangdong Provincial Key Laboratory of Orthopedics and Traumatology The First Affiliated Hospital of Sun Yat‐sen University Guangzhou 510080 ChinaState Key Laboratory of Cellular Stress Biology Fujian Provincial Key Laboratory of Organ and Tissue Regeneration School of Medicine Faculty of Medicine and Life Sciences Xiamen University Xiamen 361102 ChinaGuangdong Provincial Key Laboratory of Proteomics and State Key Laboratory of Organ Failure Research School of Basic Medical Sciences Southern Medical University Guangzhou 510515 ChinaDepartment of Spine Surgery Guangdong Provincial Key Laboratory of Orthopedics and Traumatology The First Affiliated Hospital of Sun Yat‐sen University Guangzhou 510080 ChinaDepartment of Orthopedics Renmin Hospital of Wuhan University Wuhan 430060 ChinaDepartment of Spine Surgery Guangdong Provincial Key Laboratory of Orthopedics and Traumatology The First Affiliated Hospital of Sun Yat‐sen University Guangzhou 510080 ChinaDepartment of Spine Surgery Guangdong Provincial Key Laboratory of Orthopedics and Traumatology The First Affiliated Hospital of Sun Yat‐sen University Guangzhou 510080 ChinaDepartment of Spine Surgery Guangdong Provincial Key Laboratory of Orthopedics and Traumatology The First Affiliated Hospital of Sun Yat‐sen University Guangzhou 510080 ChinaDepartment of Spine Surgery Guangdong Provincial Key Laboratory of Orthopedics and Traumatology The First Affiliated Hospital of Sun Yat‐sen University Guangzhou 510080 ChinaDepartment of Gynecology and Obstetrics The First Affiliated Hospital of Sun Yat‐sen University Guangzhou 510080 ChinaResearch Center for Translational Medicine The First Affiliated Hospital of Sun Yat‐sen University Guangzhou 510080 ChinaDepartment of Spine Surgery Guangdong Provincial Key Laboratory of Orthopedics and Traumatology The First Affiliated Hospital of Sun Yat‐sen University Guangzhou 510080 ChinaState Key Laboratory of Cellular Stress Biology Fujian Provincial Key Laboratory of Organ and Tissue Regeneration School of Medicine Faculty of Medicine and Life Sciences Xiamen University Xiamen 361102 ChinaDepartment of Spine Surgery Guangdong Provincial Key Laboratory of Orthopedics and Traumatology The First Affiliated Hospital of Sun Yat‐sen University Guangzhou 510080 ChinaAbstract The intervertebral disc (IVD) acts as a fibrocartilaginous joint to anchor adjacent vertebrae. Although several studies have demonstrated the cellular heterogeneity of adult mature IVDs, a single‐cell transcriptomic atlas mapping early IVD formation is still lacking. Here, the authors generate a spatiotemporal and single cell‐based transcriptomic atlas of human IVD formation at the embryonic stage and a comparative mouse transcript landscape. They identify two novel human notochord (NC)/nucleus pulposus (NP) clusters, SRY‐box transcription factor 10 (SOX10)+ and cathepsin K (CTSK)+, that are distributed in the early and late stages of IVD formation and they are validated by lineage tracing experiments in mice. Matrisome NC/NP clusters, T‐box transcription factor T (TBXT)+ and CTSK+, are responsible for the extracellular matrix homeostasis. The IVD atlas suggests that a subcluster of the vertebral chondrocyte subcluster might give rise to an inner annulus fibrosus of chondrogenic origin, while the fibroblastic outer annulus fibrosus preferentially expresseds transgelin and fibromodulin . Through analyzing intercellular crosstalk, the authors further find that notochordal secreted phosphoprotein 1 (SPP1) is a novel cue in the IVD microenvironment, and it is associated with IVD development and degeneration. In conclusion, the single‐cell transcriptomic atlas will be leveraged to develop preventative and regenerative strategies for IVD degeneration.https://doi.org/10.1002/advs.202206296annulus fibrosusintervertebral disc formationnotochordnucleus pulposussingle‐cell RNA sequencing |
| spellingShingle | Taifeng Zhou Yu Chen Zhiheng Liao Long Zhang Deying Su Zhuling Li Xiaoming Yang Xiaona Ke Hengyu Liu Yuyu Chen Ricong Weng Huimin Shen Caixia Xu Yong Wan Ren Xu Peiqiang Su Spatiotemporal Characterization of Human Early Intervertebral Disc Formation at Single‐Cell Resolution Advanced Science annulus fibrosus intervertebral disc formation notochord nucleus pulposus single‐cell RNA sequencing |
| title | Spatiotemporal Characterization of Human Early Intervertebral Disc Formation at Single‐Cell Resolution |
| title_full | Spatiotemporal Characterization of Human Early Intervertebral Disc Formation at Single‐Cell Resolution |
| title_fullStr | Spatiotemporal Characterization of Human Early Intervertebral Disc Formation at Single‐Cell Resolution |
| title_full_unstemmed | Spatiotemporal Characterization of Human Early Intervertebral Disc Formation at Single‐Cell Resolution |
| title_short | Spatiotemporal Characterization of Human Early Intervertebral Disc Formation at Single‐Cell Resolution |
| title_sort | spatiotemporal characterization of human early intervertebral disc formation at single cell resolution |
| topic | annulus fibrosus intervertebral disc formation notochord nucleus pulposus single‐cell RNA sequencing |
| url | https://doi.org/10.1002/advs.202206296 |
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