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Type II collagen positive (Col2+) cells have been reported to encompass early mesenchymal progenitors that continue to become chondrocytes, osteoblasts, stromal cells, and adipocytes in long bone. However, the function of Col2+ cells in spine and intervertebral disc (IVD) development is largely unknown. To further elucidate the function of Col2+ progenitors in spine, we generated the mice with ablation of Col2+ cells either at embryonic or at postnatal stage. Embryonic ablation of Col2+ progenitors caused the mouse die at newborn with the absence of all spine and IVD. Moreover, postnatal deletion Col2+ cells in spine resulted in a shorter growth plate and endplate cartilage, defected inner annulus fibrosus, a less compact and markedly decreased gel-like matrix in the nucleus pulposus and disorganized cell alignment in each compartment of IVD. Genetic lineage tracing IVD cell populations by using inducible Col2-creERT;tdTomato reporter mice and non-inducible Col2-cre;tdTomato reporter mice revealed that the numbers and differentiation ability of Col2+ progenitors decreased with age. Moreover, immunofluorescence staining showed type II collagen expression changed from extracellular matrix to cytoplasm in nucleus pulposus between 6\u00a0month and 1-year-old mice. Finally, fate-mapping studies revealed that Col2+ progenitors are essential for IVD repair in IVD injured model. In summary, embryonic Col2+ cells are the major source of spine development and Col2+ progenitors are the important contributors for IVD repair and regeneration.<\/jats:p>","DOI":"10.1002\/sctm.20-0424","type":"journal-article","created":{"date-parts":[[2021,5,25]],"date-time":"2021-05-25T11:47:45Z","timestamp":1621943265000},"page":"1419-1432","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Type II Collagen-Positive Embryonic Progenitors are the Major Contributors to Spine and Intervertebral Disc Development and Repair"],"prefix":"10.1093","volume":"10","author":[{"given":"Xinhua","family":"Li","sequence":"first","affiliation":[{"name":"Department of Basic and Translational Sciences \u00a0School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA"},{"name":"Department of Orthopedics \u00a0Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's 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