Wound healing mechanisms by distinct oral fibroblast population

项目总结 口腔创伤愈合的特点是炎症迅速消退，疤痕最小。因为它是质数 理想的组织再生的例子，有越来越多的跨学科的兴趣来研究的机制 口腔伤口愈合。成纤维细胞在这一过程中起着重要作用，也与口腔疾病有关。 造成全球经济负担高达4420亿美元。连接词的最新研究进展 组织生物学已阐明成纤维细胞异质性在真皮纤维化发病机制中的重要性 和类风湿性关节炎。然而，口腔成纤维细胞在体内的异质性，从而产生了一种功能性 口腔创伤愈合过程中选择成纤维细胞群的意义尚不清楚。在这里，我们发现 出生后的PRX1+细胞存在于小鼠牙龈中，表达成纤维细胞的共同标志。初步数据 证明富含PRX1+细胞的伤口比伤口愈合更快，炎症最小 缺乏这些细胞的生物。因此，我们将检验PRX1+细胞代表独特的口腔成纤维细胞的总体假设 祖细胞负责通过一种涉及解决 发炎。目标1将利用一种自动移植的方法，并测试移植的假设 PRX1+细胞在体内可作为间充质祖细胞促进口腔创伤愈合。目标 2将调查PRX1+细胞的谱系特异性消融是否通过快速导致失败而延迟伤口愈合 体内消炎，探讨PRX1+成纤维细胞对小鼠免疫细胞的调节机制 培养化验。在目标3中，我们将执行单细胞RNA测序来比较 在小鼠中，PRX1+丰富的口腔创伤中的间质和白细胞亚型与PRX1缺乏的创伤中的那些相比。 此外，我们将通过单细胞测序和原位检测在人牙龈中是否发现与PRX1等同的细胞 验证。完成后，拟议的研究有望揭示PRX1+细胞是促进愈合的口服细胞 成纤维细胞亚群，并通过暗示Connective的临床应用提供显著的翻译价值 富含PRX1+成纤维细胞的组织或体外干细胞疗法。

PROJECT SUMMARY Oral wound healing is characterized by rapid resolution of inflammation and minimal scarring. As it is a prime example of ideal tissue regeneration, there is a growing interdisciplinary interest in studying the mechanisms of oral wound healing. Fibroblasts play an essential role in this process and are also implicated in oral diseases responsible for the global economic burden amounting to 442 billion dollars. Recent advances in connective tissue biology have elucidated the importance of fibroblast heterogeneity in the pathogenesis of dermal fibrosis and rheumatoid arthritis. However, the in vivo heterogeneity of oral fibroblasts and thereby a functional significance of select fibroblast population during oral wound healing is poorly understood. Here, we found that postnatal Prx1+ cells are found in mouse gingiva and express common markers of fibroblasts. Preliminary data demonstrate that wounds enriched in Prx1+ cells heal faster with minimal inflammation compared to wounds that lack these cells. Therefore we will test the overall hypothesis that Prx1+ cells represent distinct oral fibroblast progenitors and are responsible for rapid tissue regeneration through a mechanism that involves resolution of inflammation. Aim 1 will utilize an auto-transplantation approach and test the hypothesis that transplanted Prx1+ cells contribute to accelerated oral wound healing by functioning as mesenchymal progenitors in vivo. Aim 2 will investigate if lineage specific ablation of Prx1+ cells delays wound healing by causing the failure to quickly resolve inflammation in vivo, and explore mechanisms of immune cell modulation by Prx1+ fibroblasts in co- culture assays. In Aim 3, we will perform single cell RNA-sequencing to compare transcriptomic profiles of mesenchymal and leukocyte cell subtypes in Prx1+ enriched oral wounds to those in Prx1-poor wounds in mice. Moreover, we will test if Prx1-equivalent cells are found in human gingiva by single cell sequencing and in situ validation. Upon completion, the proposed studies are expected to reveal Prx1+ cells as pro-healing oral fibroblast subset and provide a significant translational value by implicating the clinical utilization of connective tissues or ex vivo stem cell therapy that are enriched with Prx1+ fibroblasts.