Porciuncula Angelo, Zapata Natalia, Guruceaga Elizabeth, Agirre Xabier, Barajas Miguel, Prosper Felipe
Hematology and Cell Therapy Area, Clínica Universidad de Navarra, Avda. Pio XII 36, 31008 Pamplona, Spain.
Gene Expr Patterns. 2013 Jan-Feb;13(1-2):12-20. doi: 10.1016/j.gep.2012.08.002. Epub 2012 Sep 8.
MicroRNAs (miRNAs), small non-coding RNAs that fine-tune gene expression, play multiple roles in the cell, including cell fate specification. We have analyzed the differential expression of miRNAs during fibroblast reprogramming into induced pluripotent stem cells (iPSCs) and endoderm induction from iPSCs upon treatment with high concentrations of Activin-A. The reprogrammed iPSCs assumed an embryonic stem cell (ESC)-like miRNA signature, marked by the induction of pluripotency clusters miR-290-295 and miR-302/367 and conversely the downregulation of the let-7 family. On the other hand, endoderm induction in iPSCs resulted in the upregulation of 13 miRNAs. Given that the liver and the pancreas are common derivatives of the endoderm, analysis of the expression of these 13 upregulated miRNAs in hepatocytes and pancreatic islets revealed a tendency for these miRNAs to be expressed more in pancreatic islets than in hepatocytes. These observations provide insights into how differentiation may be guided more efficiently towards the endoderm and further into the liver or pancreas. Moreover, we also report novel miRNAs enriched for each of the cell types analyzed.
微小RNA（miRNA）是一类可微调基因表达的小型非编码RNA，在细胞中发挥多种作用，包括细胞命运的决定。我们分析了在成纤维细胞重编程为诱导多能干细胞（iPSC）过程中以及用高浓度激活素A处理iPSC诱导其向内胚层分化过程中miRNA的差异表达。重编程后的iPSC呈现出类似胚胎干细胞（ESC）的miRNA特征，其标志是多能性簇miR - 290 - 295和miR - 302/367的诱导表达，相反，let - 7家族的表达下调。另一方面，iPSC向内胚层的诱导导致13种miRNA上调。鉴于肝脏和胰腺是内胚层的常见衍生物，对这13种上调的miRNA在肝细胞和胰岛中的表达分析显示，这些miRNA在胰岛中的表达倾向于高于肝细胞。这些观察结果为如何更有效地引导细胞向内胚层分化以及进一步分化为肝脏或胰腺提供了见解。此外，我们还报告了在所分析的每种细胞类型中富集的新型miRNA。
