miR-183/96/182 cluster is an important morphogenetic factor targetingPAX6expression in differentiating human retinal organoids

• Authors: PEŠKOVÁ Lucie; JURČÍKOVÁ Denisa; VÁŇOVÁ Tereza; KŘIVÁNEK Jan; CAPANDOVÁ Michaela; ŠRÁMKOVÁ Zuzana; ŠEBESTÍKOVÁ Jana; KOLOUŠKOVÁ Magdaléna; KOTASOVÁ Hana; STREIT Libor; BÁRTA Tomáš
• Year of publication: 2020
• Type: Article in Periodical
• Magazine / Source: Stem Cells
• MU Faculty or unit: Faculty of Medicine
• Web: https://stemcellsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/stem.3272
• Doi: http://dx.doi.org/10.1002/stem.3272
• Keywords: microRNAs; organoids; pluripotent stem cells; retina
• Description: MicroRNAs (miRNAs), a class of small, noncoding 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 identifiedPAX6, 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 ofPAX6expression, but it also plays a crucial role in retinal tissue morphogenesis.

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