Open Accessmicro RNA ‐103/107 Family Regulates Multiple Epithelial Stem Cell Characteristics
Author(s) -
Peng Han,
Park Jong Kook,
Katsnelson Julia,
Kaplan Nihal,
Yang Wending,
Getsios Spiro,
Lavker Robert M.
Publication year - 2015
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1962
Subject(s) - biology , stem cell , microbiology and biotechnology , microrna , cell cycle , yap1 , focal adhesion , cadherin , cell , signal transduction , genetics , transcription factor , gene
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. S tem C ells 2015;33:1642–1656