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

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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.

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Acknowledgments

This research was supported by the MOTIE (The Ministry of Trade, Industry and Energy), Korea, under the Global collaborative R&D program (No. M0000049) supervised by the KIAT (Korea Institute for Advancement of Technology), and partially supported by the Research Institute for Veterinary Science, Seoul National University (SNU, Republic of Korea).

Conflict of Interest

The authors declare no potential conflicts of interest.

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Authors and Affiliations

  1. Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea

    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

  2. BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea

    Jin Young Lee, Byung-Chul Lee, Insung Kang & Tae-Hoon Shin

  3. Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, 151-742, Republic of Korea

    Soon Won Choi & Kyung-Sun Kang

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  1. Soon Won Choi
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Correspondence to Kyung-Sun Kang.

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Soon Won Choi and Jae-Jun Kim These authors contributed equally to this work.

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Choi, S.W., Kim, JJ., Seo, MS. et al. miR-410 Inhibition Induces RPE Differentiation of Amniotic Epithelial Stem Cells via Overexpression of OTX2 and RPE65. Stem Cell Rev and Rep 11, 376–386 (2015). https://doi.org/10.1007/s12015-014-9568-2

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