miR‐183/96/182 cluster is an important morphogenetic factor targeting PAX6 expression in differentiating human retinal organoids

Peskova L, Jurcikova D, Vanova T, Krivanek J, Capandova M, Sramkova Z, Sebestikova J, Kolouskova M, Kotasova H, Streit L, Barta T.

Stem Cells. 2020 Sep 1. doi:10.1002/stem.3272.

14 Sep 2020

MicroRNAs (miRNAs), a class of small, non-coding RNA molecules represent important regulators of gene expression. Recent reports have implicated their role in the cell specification process acting as "fine-tuners" to ensure the precise gene expression at the specific stage of cell differentiation. Here we used retinal organoids differentiated from human pluripotent stem cells (hPSCs) as a model to closely investigate the role of a sensory organ-specific and evolutionary conserved miR-183/96/182 cluster. Using a miRNA tough decoy approach, we inhibited the miR-183/96/182 cluster in hPSCs. Inhibition of the miRNA cluster resulted in an increased expansion of neuroepithelium leading to abnormal "bulged" neural retina in organoids, associated with upregulation of neural-specific and retinal-specific genes. Importantly, we identified PAX6, a well-known essential gene in neuroectoderm specification, as a target of the miR-183/96/182 cluster members. Taken together, the miR-183/96/182 cluster not only represents an important regulator of PAX6 expression, but it also plays a crucial role in retinal tissue morphogenesis. © AlphaMed Press 2020 SIGNIFICANCE STATEMENT: This study shows that the miR-183/96/182 cluster regulates PAX6 expression and its inhibition leads to increased neural retina expansion at early stages of differentiation of human retinal organoids derived from hPSCs. Our results indicate that the miR-183/96/182 cluster plays an important role in morphogenesis of the neural retina.

Keywords: microRNAs; organoids; pluripotent stem cells; retina.


Read the full story: https://stemcellsjournals.onlinelibrary.wiley.com/doi/abs/10.1002/stem.3272

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