Open AccessMicroRNA-28 potentially regulates the photoreceptor lineage commitment of Müller glia-derived progenitors
Author(s) -
Hongpei Ji,
Ye Xiong,
Wook Song,
En-Dong Zhang,
Zhaolin Gao,
Fei Yao,
Tao Su,
Rongrong Zhou,
Xiaobo Xia
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-11112-4
Subject(s) - muller glia , progenitor cell , biology , microbiology and biotechnology , photoreceptor cell , microrna , gene knockdown , sox2 , retinal , retinal regeneration , pax6 , transcription factor , rhodopsin , retina , progenitor , nestin , stem cell , regeneration (biology) , neural stem cell , cell culture , genetics , neuroscience , gene , biochemistry
Retinal degenerative diseases ultimately result into irreversible photoreceptor death or loss. At present, the most promising treatment for these diseases is cell replacement therapy. Müller glia are the major glia in the retina, displaying cardinal features of retinal progenitor cells, and can be candidate of seed cells for retinal degenerative diseases. Here, mouse retinal Müller glia dissociated and cultured in vitro amplified and were dedifferentiated into Müller glia-derived progenitors (MGDPs), demonstrating expression of stem/progenitor cell markers Nestin, Sox2 and self-renewal capacity. MicroRNAs (miRNAs) play unique roles in the retinogenesis, so we hypothesized miRNAs would contribute to photoreceptor lineage commitment of MGDPs. By TargetScan, Miranda, and Pictar bioinformatics, gain/loss-of-function models, dual luciferase assay, we identified and validated that miR-28 targeted the photoreceptor-specific CRX transcription factor. Anti-miR-28 could induce MGDPs to differentiate into neurons strongly expressing CRX and Rhodopsin, while miR-28 mimic suppressed CRX and Rhodopsin expression. Knockdown of CRX by siRNA blocked the expression of CRX and Rhodospin upregulated by anti-miR-28, indicating that anti-miR-28 potentially induced photoreceptor commitment of MGDPs by targeting CRX, but more experiments are necessary to confirm their role in differentiation.