title: miR-410 Inhibition Induces RPE Differentiation of Amniotic Epithelial Stem Cells via Overexpression of OTX2 and RPE65.
abstract: 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.
authors.affiliation: Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Soon Won
authors.initials: SW
authors.lastname: Choi
authors.forename: Jae-Jun
authors.initials: JJ
authors.lastname: Kim
authors.forename: Min-Soo
authors.initials: MS
authors.lastname: Seo
authors.forename: Sang-Bum
authors.initials: SB
authors.lastname: Park
authors.forename: Tae-Wook
authors.initials: TW
authors.lastname: Kang
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Byung-Chul
authors.initials: BC
authors.lastname: Lee
authors.forename: Insung
authors.initials: I
authors.lastname: Kang
authors.forename: Tae-Hoon
authors.initials: TH
authors.lastname: Shin
authors.forename: Hyung-Sik
authors.initials: HS
authors.lastname: Kim
authors.forename: Kyung-Rok
authors.initials: KR
authors.lastname: Yu
authors.forename: Kyung-Sun
authors.initials: KS
authors.lastname: Kang
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology; D002454:Cell Differentiation / Q000235:genetics*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D051857:Otx Transcription Factors / Q000096:biosynthesis*; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D019745:cis-trans-Isomerases / Q000096:biosynthesis*; D000099178:Retinoid Isomerohydrolase
chemical_list: D035683:MicroRNAs; D051857:Otx Transcription Factors; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; C568527:MIRN410 microRNA, human; C497659:OTX2 protein, human