Specificities of cellular uptake of primary cilium-derived extracellular vesicles for intercellular communication

纤毛疾病的细胞内在机制已经得到了很好的研究。我们研究了野生型NIH/3T3细胞培养上清液中提取的细胞外生物活性因子对原代纤毛缺陷NIH/3T3-Kif3a-KO细胞损伤后迁移/增殖的影响。与来自NIH/3T3-Kif3a-KO细胞和NIH/3T3-Dyc2h1-KO细胞原代纤毛缺陷细胞培养上清液的因子相比，野生型NIH/3T3细胞培养上清液可提高靶细胞的迁移/增殖速率。此外，通过对培养上清液的组学分析，我们发现了一个分子，显示了原代纤毛缺陷细胞培养上清液的减少。这些发现表明，成纤维细胞以一种主要纤毛依赖的方式，通过细胞-外在调节机制来调节原发纤毛缺陷靶细胞的细胞迁移/增殖过程。

Cell-intrinsic mechanisms of ciliopathies have been well studied. In contrast, cell-extrinsic factors that underlie ciliopathies have barely been explored.We investigated the effects of extracellular bioactive factors derived from wildtype NIH/3T3 cells culture supernatant on the migration/ proliferation of primary cilium-deficient NIH/3T3-Kif3a-KO cells after wounding. The factors derived from wildtype NIH/3T3 cells culture supernatant increased the rate of cell migration/proliferation in target cells as compared to the factors derived from primary cilium-deficient cells culture supernatant from NIH/3T3-Kif3a-KO cells and NIH/3T3-Dync2h1-KO cells. Furthermore, by omics analysis of the supernatants, we found a molecule that showed a decline in the culture supernatant of primary cilium-deficient cells. These findings suggest that fibroblasts regulate cellular migration/proliferation process in primary cilium-deficient target cells via cell-extrinsic regulatory mechanisms in a primary cilium-dependent manner.