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Inhibition of miR-145 Enhances Reprogramming of Human Dermal Fibroblasts to Induced Pluripotent Stem Cells

Lookup NU author(s): Dr Tomas Barta, Dr Joseph Collin, Dr Irina Neganova, Professor Lyle Armstrong, Professor Majlinda Lako

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

MicroRNA (miRNAs) are short non-coding 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 down-regulated during reprogramming process. Inhibition of miR-145 in DFs led to the induction of “cellular plasticity” demonstrated by: i) alteration of cell morphology associated with down-regulation of mesenchymal and up-regulation of epithelial markers; ii) up-regulation of pluripotency-associated genes including SOX2, KLF4, C-MYC; iii) down-regulation 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.


Publication metadata

Author(s): Barta T, Peskova L, Collin J, Montaner D, Neganova I, Armstrong L, Lako M

Publication type: Article

Publication status: Published

Journal: Stem Cells

Year: 2016

Volume: 34

Issue: 1

Pages: 246-251

Print publication date: 01/01/2016

Online publication date: 09/10/2015

Acceptance date: 24/08/2015

Date deposited: 23/09/2015

ISSN (print): 1066-5099

ISSN (electronic): 1549-4918

Publisher: AlphaMed Press

URL: http://dx.doi.org/10.1002/stem.2220

DOI: 10.1002/stem.2220

PubMed id: 26418476


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