Peng Han, Park Jong Kook, Katsnelson Julia, Kaplan Nihal, Yang Wending, Getsios Spiro, Lavker Robert M
Department of Dermatology, Northwestern University, Chicago, Illinois, USA.
Stem Cells. 2015 May;33(5):1642-56. doi: 10.1002/stem.1962.
The stem cell niche is thought to affect cell cycle quiescence, proliferative capacity, and communication between stem cells and their neighbors. How these activities are controlled is not completely understood. Here we define a microRNA family (miRs-103/107) preferentially expressed in the stem cell-enriched limbal epithelium that regulates and integrates these stem cell characteristics. miRs-103/107 target the ribosomal kinase p90RSK2, thereby arresting cells in G0/G1 and contributing to a slow-cycling phenotype. Furthermore, miRs-103/107 increase the proliferative capacity of keratinocytes by targeting Wnt3a, which enhances Sox9 and YAP1 levels and thus promotes a stem cell phenotype. This miRNA family also regulates keratinocyte cell-cell communication by targeting: (a) the scaffolding protein NEDD9, preserving E-cadherin-mediated cell adhesion; and (b) the tyrosine phosphatase PTPRM, which negatively regulates connexin 43-based gap junctions. We propose that such regulation of cell communication and adhesion molecules maintains the integrity of the stem cell niche ultimately preserving self-renewal, a hallmark of epithelial stem cells.
干细胞微环境被认为会影响细胞周期静止、增殖能力以及干细胞与其邻近细胞之间的通讯。这些活动是如何被控制的尚未完全清楚。在此，我们定义了一个在富含干细胞的角膜缘上皮中优先表达的微小RNA家族（miR-103/107），它调控并整合这些干细胞特性。miR-103/107靶向核糖体激酶p90RSK2，从而使细胞停滞在G0/G1期，并导致慢周期表型。此外，miR-103/107通过靶向Wnt3a增加角质形成细胞的增殖能力，Wnt3a可提高Sox9和YAP1水平，从而促进干细胞表型。这个微小RNA家族还通过靶向以下物质来调节角质形成细胞间的通讯：（a）支架蛋白NEDD9，维持E-钙黏蛋白介导的细胞黏附；（b）酪氨酸磷酸酶PTPRM，其负向调节基于连接蛋白43的间隙连接。我们提出，这种对细胞通讯和黏附分子的调控维持了干细胞微环境的完整性，最终保留了自我更新能力，这是上皮干细胞的一个标志。
