MicroRNA-28 potentially regulates the photoreceptor lineage commitment of Müller glia-derived progenitors.
MicroRNA-28 potentially regulates the photoreceptor lineage commitment of Müller glia-derived progenitors.
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DOI：
10.1038/s41598-017-11112-4
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发表时间：
2017-09-12
影响因子：
4.6
通讯作者：
Xia XB
中科院分区：
文献类型：
--
作者：
Ji HP;Xiong Y;Song WT;Zhang ED;Gao ZL;Yao F;Su T;Zhou RR;Xia XB
视网膜退行性疾病最终导致不可逆的光感受器死亡或丧失。目前，这些疾病最有希望的治疗方法是细胞替代疗法。米勒神经胶质细胞是视网膜中的主要神经胶质细胞，具有视网膜祖细胞的主要特征，并且可以成为视网膜退行性疾病的种子细胞候选者。在这里，小鼠视网膜穆勒神经胶质细胞在体外解离和培养，扩增并去分化为穆勒神经胶质细胞衍生的祖细胞（MGDP），证明了干/祖细胞标记物Nestin、Sox2的表达和自我更新能力。 MicroRNA (miRNA) 在视网膜发生中发挥独特的作用，因此我们假设 miRNA 将有助于 MGDP 的光感受器谱系承诺。通过 TargetScan、Miranda 和 Pictar 生物信息学、功能获得/丧失模型、双荧光素酶测定，我们鉴定并验证了 miR-28 靶向光感受器特异性 CRX 转录因子。抗miR-28可以诱导MGDP分化为强烈表达CRX和视紫红质的神经元，而miR-28模拟物则抑制CRX和视紫红质的表达。 siRNA 敲低 CRX 阻断了抗 miR-28 上调的 CRX 和 Rhodospin 表达，表明抗 miR-28 可能通过靶向 CRX 诱导 MGDP 的光感受器承诺，但需要更多的实验来证实它们在分化中的作用。
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.
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影响因子：
12.3
作者：
Ruzycki PA;Tran NM;Kefalov VJ;Kolesnikov AV;Chen S
通讯作者：
Chen S
影响因子：
5.3
作者：
Cremisi F
通讯作者：
Cremisi F
DOI：
10.1002/dvdy.24375
发表时间：
2016-07
期刊：
Developmental dynamics : an official publication of the American Association of Anatomists
影响因子：
--
作者：
Hamon A;Roger JE;Yang XJ;Perron M
通讯作者：
Perron M
影响因子：
5.3
作者：
Bernardos, Rebecca L.;Barthel, Linda K.;Raymond, Pamela A.
通讯作者：
Raymond, Pamela A.
影响因子：
4.4
作者：
Jomary, Catherine;Jones, Stephen E.
通讯作者：
Jones, Stephen E.