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.; Kolouskova, M.; Kotasova, H.; Streit, L.; Barta, T.

doi:10.1101/2020.04.01.019539

bioRxiv · 10.1101/2020.04.01.019539

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.·Kolouskova, M.·Kotasova, H.·Streit, L.·Barta, T.

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Abstract

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.

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Peskova, L., Jurcikova, D., Vanova, T., Krivanek, J., Capandova, M., Sramkova, Z., Kolouskova, M., Kotasova, H., Streit, L., Barta, T.. 2020-04-02. miR-183/96/182 cluster is an important morphogenetic factor targeting PAX6 expression in differentiating human retinal organoids. https://doi.org/10.1101/2020.04.01.019539

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