Publication details

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

Citation
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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