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

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

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. H...

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Published in:Stem cells (Dayton, Ohio) Vol. 38; no. 12; pp. 1557 - 1567
Main Authors: Peskova, Lucie, Jurcikova, Denisa, Vanova, Tereza, Krivanek, Jan, Capandova, Michaela, Sramkova, Zuzana, Sebestikova, Jana, Kolouskova, Magdalena, Kotasova, Hana, Streit, Libor, Barta, Tomas
Format: Journal Article
Language:English
Published: Hoboken, USA John Wiley & Sons, Inc 01-12-2020
Oxford University Press
Subjects:
Cell differentiation
Clusters
Differentiation (biology)
Evolutionary conservation
Gene expression
MicroRNAs
miRNA
Morphogenesis
Neuroectoderm
Organoids
Pax6 protein
Pluripotency
pluripotent stem cells
Retina
Sense organs
Specifications
Stem cells
Tuners
microRNAs
pluripotent stem cells
retina
organoids
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Summary: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 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. Inhibition of the miR‐183/96/182 cluster in human pluripotent stem cells leads to the generation of abnormal retinal organoids.
Bibliography:Funding information
MEYS CR, Grant/Award Number: LM2018129; Czech‐BioImaging large RI project; European Regional Development Fund ‐ Project INBIO, Grant/Award Number: CZ.02.1.01/0.0/0.0/16_026/0008451; Grant Agency of Masaryk University (GAMU), Grant/Award Number: MUNI/G/1391/2018; Faculty of Medicine MU; Brno Ph.D. Talent
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ISSN:1066-5099
1549-4918
DOI:10.1002/stem.3272