Open AccessBrief Report: Inhibition of miR‐145 Enhances Reprogramming of Human Dermal Fibroblasts to Induced Pluripotent Stem Cells
Author(s) -
Barta Tomas,
Peskova Lucie,
Collin Joseph,
Montaner David,
Neganova Irina,
Armstrong Lyle,
Lako Majlinda
Publication year - 2016
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2220
Subject(s) - reprogramming , klf4 , induced pluripotent stem cell , sox2 , downregulation and upregulation , biology , microbiology and biotechnology , somatic cell , stem cell , microrna , cellular differentiation , cancer research , cell , embryonic stem cell , genetics , gene
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. S tem C ells 2016;34:246–251