miR-183/96/182 cluster is an important morphogenetic factor targeting PAX6 expression in differentiating human retinal organoids
Status Publisher Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic
Typ dokumentu časopisecké články
Grantová podpora
LM2018129
MEYS CR
Czech-BioImaging large RI project
CZ.02.1.01/0.0/0.0/16_026/0008451
European Regional Development Fund - Project INBIO
MUNI/G/1391/2018
Grant Agency of Masaryk University (GAMU)
Faculty of Medicine MU
Brno Ph.D. Talent
PubMed
32875669
DOI
10.1002/stem.3272
Knihovny.cz E-zdroje
- Klíčová slova
- microRNAs, organoids, pluripotent stem cells, retina,
- Publikační typ
- časopisecké články MeSH
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.
CEITEC Central European Institute of Technology Masaryk University Brno Czech Republic
Department of Histology and Embryology Faculty of Medicine Masaryk University Brno Czech Republic
Department of Plastic and Aesthetic Surgery St Anne's University Hospital Brno Brno Czech Republic
Institute of Experimental Biology Faculty of Science Masaryk University Brno Czech Republic
International Clinical Research Center St Anne's University Hospital Brno Czech Republic
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