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

该研究计划的总体目标是揭示调节口腔/牙周神经沟来源的基质干细胞(NCSSCs)的生态位和功能的机制。NCSSCs保留在成人组织中的几个特定位置--如骨髓、毛囊和口腔粘膜--而且它们的数量通常随着年龄的增长而下降。利用WNT1-CRE/R26RYFP报告小鼠，我们通过示踪实验表明，牙龈NCSSCs在牙周结缔组织中丰富。有趣的是，NCSSCs集中在结缔组织乳头，更具体地说，是在靠近牙龈口腔上皮细胞(OECs)的地方。众所周知，结缔组织和上皮细胞参与了分子串扰，可以调节这两种细胞的功能。因此，OECs和NCSSCs之间的串扰可能参与了NCSSC生态位和功能的调节。文献中没有关于OEC如何调控NCSSC利基或命运的信息。在本研究中，我们提出了一种新的范式，即嗅鞘细胞释放参与调控NCSSC命运的胞外小泡。

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.