title: MicroRNA signatures of iPSCs and endoderm-derived tissues.
abstract: 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.
authors.affiliation: Hematology and Cell Therapy Area, Clínica Universidad de Navarra, Avda. Pio XII 36, 31008 Pamplona, Spain. angelop@unav.es
authors.forename: Angelo
authors.initials: A
authors.lastname: Porciuncula
authors.forename: Natalia
authors.initials: N
authors.lastname: Zapata
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Guruceaga
authors.forename: Xabier
authors.initials: X
authors.lastname: Agirre
authors.forename: Miguel
authors.initials: M
authors.lastname: Barajas
authors.forename: Felipe
authors.initials: F
authors.lastname: Prosper
mesh_terms: D028341:Activins / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation; D065150:Cellular Reprogramming / Q000187:drug effects; D004707:Endoderm / Q000166:cytology / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs; C422405:activin A; D028341:Activins