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Identification of miRNAs Involved in Reprogramming Acinar Cells into Insulin Producing Cells

Reprogramming acinar cells into insulin producing cells using adenoviral (Ad)-mediated delivery of Pdx1, Ngn3 and MafA (PNM) is an innovative approach for the treatment of diabetes. Here, we aimed to investigate the molecular mechanisms involved in this process and in particular, the role of microRN...

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Autores principales: Teichenne, Joan, Morró, Meritxell, Casellas, Alba, Jimenez, Veronica, Tellez, Noelia, Leger, Adrien, Bosch, Fatima, Ayuso, Eduard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4686894/
https://www.ncbi.nlm.nih.gov/pubmed/26690959
http://dx.doi.org/10.1371/journal.pone.0145116
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author Teichenne, Joan
Morró, Meritxell
Casellas, Alba
Jimenez, Veronica
Tellez, Noelia
Leger, Adrien
Bosch, Fatima
Ayuso, Eduard
author_facet Teichenne, Joan
Morró, Meritxell
Casellas, Alba
Jimenez, Veronica
Tellez, Noelia
Leger, Adrien
Bosch, Fatima
Ayuso, Eduard
author_sort Teichenne, Joan
collection PubMed
description Reprogramming acinar cells into insulin producing cells using adenoviral (Ad)-mediated delivery of Pdx1, Ngn3 and MafA (PNM) is an innovative approach for the treatment of diabetes. Here, we aimed to investigate the molecular mechanisms involved in this process and in particular, the role of microRNAs. To this end, we performed a comparative study of acinar-to-β cell reprogramming efficiency in the rat acinar cell line AR42J and its subclone B13 after transduction with Ad-PNM. B13 cells were more efficiently reprogrammed than AR42J cells, which was demonstrated by a strong activation of β cell markers (Ins1, Ins2, IAPP, NeuroD1 and Pax4). miRNome panels were used to analyze differentially expressed miRNAs in acinar cells under four experimental conditions (i) non-transduced AR42J cells, (ii) non-transduced B13 cells, (iii) B13 cells transduced with Ad-GFP vectors and (iv) B13 cells transduced with Ad-PNM vectors. A total of 59 miRNAs were found to be differentially expressed between non-transduced AR42J and B13 cells. Specifically, the miR-200 family was completely repressed in B13 cells, suggesting that these cells exist in a less differentiated state than AR42J cells and as a consequence they present a greater plasticity. Adenoviral transduction per se induced dedifferentiation of acinar cells and 11 miRNAs were putatively involved in this process, whereas 8 miRNAs were found to be associated with PNM expression. Of note, Ad-PNM reprogrammed B13 cells presented the same levels of miR-137-3p, miR-135a-5p, miR-204-5p and miR-210-3p of those detected in islets, highlighting their role in the process. In conclusion, this study led to the identification of miRNAs that might be of compelling importance to improve acinar-to-β cell conversion for the future treatment of diabetes.
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spelling pubmed-46868942016-01-07 Identification of miRNAs Involved in Reprogramming Acinar Cells into Insulin Producing Cells Teichenne, Joan Morró, Meritxell Casellas, Alba Jimenez, Veronica Tellez, Noelia Leger, Adrien Bosch, Fatima Ayuso, Eduard PLoS One Research Article Reprogramming acinar cells into insulin producing cells using adenoviral (Ad)-mediated delivery of Pdx1, Ngn3 and MafA (PNM) is an innovative approach for the treatment of diabetes. Here, we aimed to investigate the molecular mechanisms involved in this process and in particular, the role of microRNAs. To this end, we performed a comparative study of acinar-to-β cell reprogramming efficiency in the rat acinar cell line AR42J and its subclone B13 after transduction with Ad-PNM. B13 cells were more efficiently reprogrammed than AR42J cells, which was demonstrated by a strong activation of β cell markers (Ins1, Ins2, IAPP, NeuroD1 and Pax4). miRNome panels were used to analyze differentially expressed miRNAs in acinar cells under four experimental conditions (i) non-transduced AR42J cells, (ii) non-transduced B13 cells, (iii) B13 cells transduced with Ad-GFP vectors and (iv) B13 cells transduced with Ad-PNM vectors. A total of 59 miRNAs were found to be differentially expressed between non-transduced AR42J and B13 cells. Specifically, the miR-200 family was completely repressed in B13 cells, suggesting that these cells exist in a less differentiated state than AR42J cells and as a consequence they present a greater plasticity. Adenoviral transduction per se induced dedifferentiation of acinar cells and 11 miRNAs were putatively involved in this process, whereas 8 miRNAs were found to be associated with PNM expression. Of note, Ad-PNM reprogrammed B13 cells presented the same levels of miR-137-3p, miR-135a-5p, miR-204-5p and miR-210-3p of those detected in islets, highlighting their role in the process. In conclusion, this study led to the identification of miRNAs that might be of compelling importance to improve acinar-to-β cell conversion for the future treatment of diabetes. Public Library of Science 2015-12-21 /pmc/articles/PMC4686894/ /pubmed/26690959 http://dx.doi.org/10.1371/journal.pone.0145116 Text en © 2015 Teichenne et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Teichenne, Joan
Morró, Meritxell
Casellas, Alba
Jimenez, Veronica
Tellez, Noelia
Leger, Adrien
Bosch, Fatima
Ayuso, Eduard
Identification of miRNAs Involved in Reprogramming Acinar Cells into Insulin Producing Cells
title Identification of miRNAs Involved in Reprogramming Acinar Cells into Insulin Producing Cells
title_full Identification of miRNAs Involved in Reprogramming Acinar Cells into Insulin Producing Cells
title_fullStr Identification of miRNAs Involved in Reprogramming Acinar Cells into Insulin Producing Cells
title_full_unstemmed Identification of miRNAs Involved in Reprogramming Acinar Cells into Insulin Producing Cells
title_short Identification of miRNAs Involved in Reprogramming Acinar Cells into Insulin Producing Cells
title_sort identification of mirnas involved in reprogramming acinar cells into insulin producing cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4686894/
https://www.ncbi.nlm.nih.gov/pubmed/26690959
http://dx.doi.org/10.1371/journal.pone.0145116
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