PT  - JOURNAL ARTICLE
AU  - Lucie Peskova
AU  - Denisa Jurcikova
AU  - Tereza Vanova
AU  - Jan Krivanek
AU  - Michaela Capandova
AU  - Zuzana Sramkova
AU  - Magdalena Kolouskova
AU  - Hana Kotasova
AU  - Libor Streit
AU  - Tomas Barta
TI  - miR-183/96/182 cluster is an important morphogenetic factor targeting <em>PAX6</em> expression in differentiating human retinal organoids
AID  - 10.1101/2020.04.01.019539
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.04.01.019539
4099  - http://biorxiv.org/content/early/2020/04/02/2020.04.01.019539.short
4100  - http://biorxiv.org/content/early/2020/04/02/2020.04.01.019539.full
AB  - 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.