Type II collagen-positive embryonic progenitors are the major contributors to spine and intervertebral disc development and repair,STEM CELLS Translational Medicine

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Type II collagen-positive embryonic progenitors are the major contributors to spine and intervertebral disc development and repair
STEM CELLS Translational Medicine ( IF 5.4 ) Pub Date : 2021-05-25 , DOI: 10.1002/sctm.20-0424
Xinhua Li _{1,

2,

3} , Shuting Yang ₁ , Ling Qin ₄ , Shuying Yang _{1,

5,

6}

Affiliation

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.

中文翻译：

II型胶原蛋白阳性胚胎祖细胞是脊柱和椎间盘发育和修复的主要贡献者

脊柱发育的基本机制知之甚少。据报道，II 型胶原蛋白阳性 (Col2+) 细胞包括早期间充质祖细胞，这些祖细胞继续成为长骨中的软骨细胞、成骨细胞、基质细胞和脂肪细胞。然而，Col2+ 细胞在脊柱和椎间盘 (IVD) 发育中的功能在很大程度上是未知的。为了进一步阐明 Col2+ 祖细胞在脊柱中的功能，我们在胚胎或出生后阶段产生了消融 Col2+ 细胞的小鼠。Col2+ 祖细胞的胚胎消融导致小鼠在新生儿时死亡，所有脊柱和体外诊断均不存在。此外，脊柱中的出生后缺失 Col2+ 细胞导致生长板和终板软骨变短，内纤维环缺损，髓核中的凝胶样基质不太紧凑且显着减少，IVD 的每个隔室中的细胞排列紊乱。使用诱导型 Col2-creERT;tdTomato 报告小鼠和非诱导型 Col2-cre;tdTomato 报告小鼠的遗传谱系追踪 IVD 细胞群显示 Col2+ 祖细胞的数量和分化能力随着年龄的增长而下降。此外，免疫荧光染色显示 6 个月至 1 岁小鼠髓核中 II 型胶原蛋白表达从细胞外基质变为细胞质。最后，命运映射研究表明，Col2+ 祖细胞对于 IVD 损伤模型中的 IVD 修复至关重要。总之，胚胎Col2+细胞是脊柱发育的主要来源，Col2+祖细胞是IVD修复和再生的重要贡献者。

更新日期：2021-05-25

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