Brief Report: Inhibition of miR-145 Enhances Reprogramming of Human Dermal Fibroblasts to Induced Pluripotent Stem Cells.
Brief Report: Inhibition of miR-145 Enhances Reprogramming of Human Dermal Fibroblasts to Induced Pluripotent Stem Cells.
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DOI：
10.1002/stem.2220
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发表时间：
2016-01
期刊：
影响因子：
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通讯作者：
Lako M
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文献类型：
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作者：
Barta T;Peskova L;Collin J;Montaner D;Neganova I;Armstrong L;Lako M
microRNA（miRNAs）是一类参与多种细胞过程的非编码RNA分子，在体细胞重编程中起重要作用。我们进行了基于阵列的筛选以鉴定在真皮皮肤成纤维细胞（DF）和诱导多能干细胞（iPSC）之间差异表达的候选物。我们将研究集中在miR-145上，并表明该候选物相对于iPSC在DF中高度表达，并在重编程过程中显著下调。在DF中抑制miR-145导致诱导“细胞可塑性”，这通过以下方式证明：（a）与间充质下调和上皮标志物上调相关的细胞形态改变;（B）多能性相关基因（包括SOX 2、KLF 4、C-MYC）上调;（c）已知抑制重编程的miRNA let-7 B下调;和（iv）在重编程因子存在下重编程为iPSC的效率增加。总之，我们的结果表明miR-145与体细胞重编程为iPSC的分子途径之间存在直接的功能联系。干细胞2016;34：246-251
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