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Brief Report: Inhibition of miR‐145 Enhances Reprogramming of Human Dermal Fibroblasts to Induced Pluripotent Stem Cells

MicroRNA (miRNAs) are short noncoding RNA molecules involved in many cellular processes and shown to play a key role in somatic cell induced reprogramming. We performed an array based screening to identify candidates that are differentially expressed between dermal skin fibroblasts (DFs) and induced...

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Autores principales: Barta, Tomas, Peskova, Lucie, Collin, Joseph, Montaner, David, Neganova, Irina, Armstrong, Lyle, Lako, Majlinda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4982107/
https://www.ncbi.nlm.nih.gov/pubmed/26418476
http://dx.doi.org/10.1002/stem.2220
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author Barta, Tomas
Peskova, Lucie
Collin, Joseph
Montaner, David
Neganova, Irina
Armstrong, Lyle
Lako, Majlinda
author_facet Barta, Tomas
Peskova, Lucie
Collin, Joseph
Montaner, David
Neganova, Irina
Armstrong, Lyle
Lako, Majlinda
author_sort Barta, Tomas
collection PubMed
description MicroRNA (miRNAs) are short noncoding RNA molecules involved in many cellular processes and shown to play a key role in somatic cell induced reprogramming. We performed an array based screening to identify candidates that are differentially expressed between dermal skin fibroblasts (DFs) and induced pluripotent stem cells (iPSCs). We focused our investigations on miR‐145 and showed that this candidate is highly expressed in DFs relative to iPSCs and significantly downregulated during reprogramming process. Inhibition of miR‐145 in DFs led to the induction of “cellular plasticity” demonstrated by: (a) alteration of cell morphology associated with downregulation of mesenchymal and upregulation of epithelial markers; (b) upregulation of pluripotency‐associated genes including SOX2, KLF4, C‐MYC; (c) downregulation of miRNA let‐7b known to inhibit reprogramming; and (iv) increased efficiency of reprogramming to iPSCs in the presence of reprogramming factors. Together, our results indicate a direct functional link between miR‐145 and molecular pathways underlying reprogramming of somatic cells to iPSCs. Stem Cells 2016;34:246–251
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spelling pubmed-49821072016-08-26 Brief Report: Inhibition of miR‐145 Enhances Reprogramming of Human Dermal Fibroblasts to Induced Pluripotent Stem Cells Barta, Tomas Peskova, Lucie Collin, Joseph Montaner, David Neganova, Irina Armstrong, Lyle Lako, Majlinda Stem Cells Embryonic Stem Cells/Induced Pluripotent Stem Cells MicroRNA (miRNAs) are short noncoding RNA molecules involved in many cellular processes and shown to play a key role in somatic cell induced reprogramming. We performed an array based screening to identify candidates that are differentially expressed between dermal skin fibroblasts (DFs) and induced pluripotent stem cells (iPSCs). We focused our investigations on miR‐145 and showed that this candidate is highly expressed in DFs relative to iPSCs and significantly downregulated during reprogramming process. Inhibition of miR‐145 in DFs led to the induction of “cellular plasticity” demonstrated by: (a) alteration of cell morphology associated with downregulation of mesenchymal and upregulation of epithelial markers; (b) upregulation of pluripotency‐associated genes including SOX2, KLF4, C‐MYC; (c) downregulation of miRNA let‐7b known to inhibit reprogramming; and (iv) increased efficiency of reprogramming to iPSCs in the presence of reprogramming factors. Together, our results indicate a direct functional link between miR‐145 and molecular pathways underlying reprogramming of somatic cells to iPSCs. Stem Cells 2016;34:246–251 John Wiley and Sons Inc. 2015-10-09 2016-01 /pmc/articles/PMC4982107/ /pubmed/26418476 http://dx.doi.org/10.1002/stem.2220 Text en © 2015 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Embryonic Stem Cells/Induced Pluripotent Stem Cells
Barta, Tomas
Peskova, Lucie
Collin, Joseph
Montaner, David
Neganova, Irina
Armstrong, Lyle
Lako, Majlinda
Brief Report: Inhibition of miR‐145 Enhances Reprogramming of Human Dermal Fibroblasts to Induced Pluripotent Stem Cells
title Brief Report: Inhibition of miR‐145 Enhances Reprogramming of Human Dermal Fibroblasts to Induced Pluripotent Stem Cells
title_full Brief Report: Inhibition of miR‐145 Enhances Reprogramming of Human Dermal Fibroblasts to Induced Pluripotent Stem Cells
title_fullStr Brief Report: Inhibition of miR‐145 Enhances Reprogramming of Human Dermal Fibroblasts to Induced Pluripotent Stem Cells
title_full_unstemmed Brief Report: Inhibition of miR‐145 Enhances Reprogramming of Human Dermal Fibroblasts to Induced Pluripotent Stem Cells
title_short Brief Report: Inhibition of miR‐145 Enhances Reprogramming of Human Dermal Fibroblasts to Induced Pluripotent Stem Cells
title_sort brief report: inhibition of mir‐145 enhances reprogramming of human dermal fibroblasts to induced pluripotent stem cells
topic Embryonic Stem Cells/Induced Pluripotent Stem Cells
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4982107/
https://www.ncbi.nlm.nih.gov/pubmed/26418476
http://dx.doi.org/10.1002/stem.2220
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