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Xiaohuan Xia, Iqbal Ahmad; Involvement of miRNAs in the regulation of Retinal Stem Cells. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2215. doi: https://doi.org/.
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MicroRNAs (miRNAs) are highly conserved small RNA molecules, which inhibit gene expression by binding to the 3’ UTR of transcripts. These miRNAs display a temporal pattern of expression in the developing retina suggesting their involvement in the maintenance and differentiation of retinal stem cells. Here, we have examined the roles of let-7 and miR-124 in the regulation of retinal stem cells.
miRNAs and their involvement were evaluated in neurosphere assay of E18 retinal progenitors. Their levels were examined in neurospheres in the presence of EGF (proliferation condition) and when shifted to a culture condition (postnatal day 1 conditional medium, BMP4, Retinoid acid, DAPT, Taurine) that facilitated rod photoreceptor differentiation. Levels of miRNA targets, Lin28, Hmga2, REST, and that of rod photoreceptor regulator, Nrl were examined in proliferation and differentiation conditions.
We observed that the levels of Hmga2, Lin28 and REST, the putative regulators of retinal stem cells, were highest in proliferating neurospheres and decreased steadily in differentiation condition. In contrast, the levels of let-7 and miR-124, which were lowest in proliferating neurospheres, increased with the time in differentiation condition, in correspondence with the levels of Nrl and rhodopsin. Such inverse correlation of miRNAs and their targets expression was also observed during retinal development in vivo. Together, these observations suggest that the let-7-Hmga2/Lin28 and miR-124/REST axes might play a role in the regulation of retinal stem cells.
miRNAs influence the fate of retinal stem cells by temporally regulating the key factors involved in their maintenance and differentiation.
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