Single-cell analysis reveals a nestin(+) tendon stem/progenitor cell population with strong tenogenic potentiality.
Single-cell analysis reveals a nestin(+) tendon stem/progenitor cell population with strong tenogenic potentiality.
复制标题
单细胞分析揭示了巢蛋白（nestin）肌腱干/祖细胞群具有强大的肌腱形成潜力
DOI：
10.1126/sciadv.1600874
复制
发表时间：
2016-11
期刊：
影响因子：
13.6
通讯作者：
Ouyang HW
中科院分区：
文献类型：
--
作者：
Yin Z;Hu JJ;Yang L;Zheng ZF;An CR;Wu BB;Zhang C;Shen WL;Liu HH;Chen JL;Heng BC;Guo GJ;Chen X;Ouyang HW
Nestin 定义了一种具有高肌腱形成潜力的新型肌腱干/祖细胞亚群。由于我们对肌腱干细胞和肌腱发生调节的了解有限，受伤肌腱的修复仍然是一项艰巨的临床挑战。通过单细胞分析来表征从肌腱组织中分离出的单个细胞的基因表达谱，在肌腱细胞群中鉴定出了巢蛋白+肌腱干/祖细胞（TSPC）的亚群。使用基因表达综合数据集和免疫荧光测定，我们发现巢蛋白表达在肌腱发育的特定阶段被激活。此外，与巢蛋白- TSPC 相比，分离的巢蛋白+ TSPC 表现出优异的肌腱形成能力。 TSPC 中巢蛋白表达的敲低抑制了它们的克隆形成能力，并在体外和体内显着降低了它们的肌腱形成潜力。因此，这些发现为识别 TSPC 亚群提供了新的见解，并说明了巢蛋白在 TSPC 命运决定和表型维持中的关键作用，这可能有助于未来治疗肌腱疾病的治疗策略。
Nestin defines a novel tendon stem/progenitor cell subpopulation with high tenogenesis potential. The repair of injured tendons remains a formidable clinical challenge because of our limited understanding of tendon stem cells and the regulation of tenogenesis. With single-cell analysis to characterize the gene expression profiles of individual cells isolated from tendon tissue, a subpopulation of nestin+ tendon stem/progenitor cells (TSPCs) was identified within the tendon cell population. Using Gene Expression Omnibus datasets and immunofluorescence assays, we found that nestin expression was activated at specific stages of tendon development. Moreover, isolated nestin+ TSPCs exhibited superior tenogenic capacity compared to nestin− TSPCs. Knockdown of nestin expression in TSPCs suppressed their clonogenic capacity and reduced their tenogenic potential significantly both in vitro and in vivo. Hence, these findings provide new insights into the identification of subpopulations of TSPCs and illustrate the crucial roles of nestin in TSPC fate decisions and phenotype maintenance, which may assist in future therapeutic strategies to treat tendon disease.