Regulation of neural crest derived progenitor cell niche by epithelial cell derived extracellular vesicles

这项研究计划的总体目标是解开调节口腔/牙龈神经嵴来源的基质干细胞（NCSCs）的生态位和功能的机制。NCSCs保留在成人组织中的一些特定位置，如骨髓、毛囊和口腔粘膜，它们的数量通常随着年龄的增长而下降。使用Wnt 1-CRE/R26 RYFP报告小鼠，我们已经使用追踪实验表明牙龈NCSCs富集在牙龈结缔组织中。有趣的是，NCSCs在结缔组织乳头处富集，更具体地说，在牙龈口腔上皮细胞（OEC）附近富集。众所周知，结缔组织和上皮细胞参与分子串扰，可以调节两种细胞类型的功能。因此，OECs和NCSSC之间的串扰可能参与NCSSC生态位和功能的调节。文献中没有关于东加勒比国家组织如何管理全国小岛屿发展中国家委员会的利基或命运的资料。在本提案中，我们提出了一个新的范例，即OECs释放细胞外囊泡，参与调节NCSSC的命运。

The overall goal of this research program is to unravel the mechanisms that regulate the niche and function of oral/gingival neural crest derived stromal stem cells (NCSSCs). The NCSSCs are retained in a few specific locations—such as bone marrow, hair follicles and oral mucosa—in adult tissue and their numbers generally decline with age. Using Wnt1-CRE/R26RYFP reporter mice, we have shown using tracing experiments that gingival NCSSCs are enriched in the gingival connective tissue. Interestingly, the NCSSCs are enriched at the connective tissue papilla and more specifically in close proximity to gingival oral epithelial cells (OECs). It is well known that connective tissue and epithelial cells engage in molecular crosstalk that can regulate the functions of both cell types. The crosstalk between OECs and NCSSCs is, therefore, likely to be involved in the regulation of NCSSC niche and function. There is no information available in the literature on how OECs could regulate NCSSC niche or fate. In the present proposal, we are proposing a new paradigm that OECs release extracellular vesicles that participate in the regulation of NCSSC fate.