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Int. J. Mol. Sci. 2018, 19(4), 1170; https://doi.org/10.3390/ijms19041170

MicroRNA Expression Analysis of In Vitro Dedifferentiated Human Pancreatic Islet Cells Reveals the Activation of the Pluripotency-Related MicroRNA Cluster miR-302s

1
Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, 53100 Siena, Italy
2
Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
*
Author to whom correspondence should be addressed.
Received: 19 March 2018 / Revised: 6 April 2018 / Accepted: 9 April 2018 / Published: 12 April 2018
(This article belongs to the Special Issue The Role of MicroRNAs in Human Diseases)
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Abstract

β-cell dedifferentiation has been recently suggested as an additional mechanism contributing to type-1 and to type-2 diabetes pathogenesis. Moreover, several studies demonstrated that in vitro culture of native human pancreatic islets derived from non-diabetic donors resulted in the generation of an undifferentiated cell population. Additional evidence from in vitro human β-cell lineage tracing experiments, demonstrated that dedifferentiated cells derive from β-cells, thus representing a potential in vitro model of β-cell dedifferentiation. Here, we report the microRNA expression profiles analysis of in vitro dedifferentiated islet cells in comparison to mature human native pancreatic islets. We identified 13 microRNAs upregulated and 110 downregulated in islet cells upon in vitro dedifferentiation. Interestingly, among upregulated microRNAs, we observed the activation of microRNA miR-302s cluster, previously defined as pluripotency-associated. Bioinformatic analysis indicated that miR-302s are predicted to target several genes involved in the control of β-cell/epithelial phenotype maintenance; accordingly, such genes were downregulated upon human islet in vitro dedifferentiation. Moreover, we uncovered that cell–cell contacts are needed to maintain low/null expression levels of miR-302. In conclusion, we showed that miR-302 microRNA cluster genes are involved in in vitro dedifferentiation of human pancreatic islet cells and inhibits the expression of multiple genes involved in the maintenance of β-cell mature phenotype. View Full-Text
Keywords: human pancreatic islets; dedifferentiation; microRNA; miR-302 human pancreatic islets; dedifferentiation; microRNA; miR-302
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Sebastiani, G.; Grieco, G.E.; Brusco, N.; Ventriglia, G.; Formichi, C.; Marselli, L.; Marchetti, P.; Dotta, F. MicroRNA Expression Analysis of In Vitro Dedifferentiated Human Pancreatic Islet Cells Reveals the Activation of the Pluripotency-Related MicroRNA Cluster miR-302s. Int. J. Mol. Sci. 2018, 19, 1170.

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