miR-410 Inhibition Induces RPE Differentiation of Amniotic Epithelial Stem Cells via Overexpression of OTX2 and RPE65

• DOI: 10.1007/s12015-014-9568-2
• Publication Date: 2014-10-28T06:48:32Z
• Authors: Soon Won Choi; Jae-Jun Kim; Min-Soo Seo; Sang-Bum Park; Tae-Wook Kang; Jin Young Lee; Byung-Chul Lee; Insung Kang; Tae-Hoon Shin; Hyung-Sik Kim; Kyung-Rok Yu; Kyung-Sun Kang
• Keywords: cis-trans-Isomerases; 0301 basic medicine; Otx Transcription Factors; Stem Cells; 4. Education; Gene Expression Regulation, Developmental; Cell Differentiation; Epithelial Cells; Retinal Pigment Epithelium; Amniotic Fluid; 3. Good health; MicroRNAs; 03 medical and health sciences; Humans

The retinal pigment epithelium (RPE) is a highly specialized cell type located between the choroid and neural retina of the eye. RPE degeneration causes irreversible visual impairment, extending to blindness. Cell therapy has recently emerged as a potential therapeutic approach for retinal degeneration. MicroRNA-based differentiation of stem cells is a new strategy for producing tissue-specific cell types. In this study, we developed a novel microRNA-based strategy for RPE induction from human amniotic epithelial stem cells (AESCs). We identified microRNAs involved in RPE development in AESCs. Of 29 putative human RPE-relevant microRNAs, microRNA-410 (miR-410) was predicted to target multiple RPE development-relevant genes. Inhibition of miR-410 induces overexpression of immature and mature RPE-specific factors, including OTX2, RPE65, Bestrophin and EMMPRIN. These RPE-like cells were morphologically altered toward a cobblestone-like shape and were able to phagocytize microbeads. We showed that miR-410 directly regulates predicted target genes OTX2 and RPE65. Our microRNA-based strategy demonstrated RPE differentiation in AESCs by treatment of an antisense microRNA-410 (anti-miR-410), without the use of additional factors or exogenous transduction. These findings suggest that miR-410 inhibition can be a useful tool for directed cell differentiation and an attractive method for cell therapy in human retinal degenerative diseases.