Direct cell fate conversion of human somatic stem cells into cone and rod photoreceptor-like cells by inhibition of microRNA-203
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Soon Won Choi1,2,*, Ji-Hee Shin1,2,*, Jae-Jun Kim1,2, Tae-Hoon Shin1,2, Yoojin Seo1,2, Hyung-Sik Kim1,3,4, Kyung-Sun Kang1,2
1Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea
2Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea
3Pusan National University School of Medicine, Busan 49241, Republic of Korea
4Biomedical Research Institute, Pusan National University Hospital, Busan 49241, Republic of Korea
*These authors contributed equally to this work
Kyung-Sun Kang, email: email@example.com
Keywords: miR-203, photoreceptor, neural retina, AESC, UCB-MSC
Received: January 07, 2016 Accepted: May 12, 2016 Published: June 07, 2016
Stem cell-based photoreceptor differentiation strategies have been the recent focus of therapies for retinal degenerative diseases. Previous studies utilized embryonic stem (ES) cells and neural retina differentiation cocktails, including DKK1 and Noggin. Here, we show a novel microRNA-mediated strategy of retina differentiation from somatic stem cells, which are potential allogeneic cell sources. Human amniotic epithelial stem cells (AESCs) and umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) treated with a retina differentiation cocktail induced gene expressions of retina development-relevant genes. Furthermore, microRNA-203 (miR-203) is abundantly expressed in human AESCs and human UCB-MSCs. This miR-203 is predicted to target multiple retina development-relevant genes, particularly DKK1, CRX, RORβ, NEUROD1, NRL and THRB. The inhibition of miR-203 induced a retina differentiation of AESCs and UCB-MSCs. Moreover, successive treatments of anti-miR-203 led to the expression of both mature photoreceptor (PR) markers, rhodopsin and opsin. In addition, we determined that CRX, NRL and DKK1 are direct targets of miR-203 using a luciferase assay. Thus, the work presented here suggests that somatic stem cells can potentially differentiate into neural retina cell types when treated with anti-miR-203. They may prove to be a source of both PR subtypes for future allogeneic stem cell-based therapies of non-regenerative retina diseases.
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