Type II collagen‐positive embryonic progenitors are the major contributors to spine and intervertebral disc development and repair

• Main Authors: Xinhua Li, Shuting Yang, Ling Qin, Shuying Yang
• Format: Article
• Language: English
• Published: Wiley 2021-10-01
• Series: Stem Cells Translational Medicine
• Subjects: intervertebral disc; lineage‐tracing; nucleus pulposus; stem cell; type II collagen
• Online Access: https://doi.org/10.1002/sctm.20-0424

Abstract Basic mechanism of spine development is poorly understood. 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 month 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.