title: microRNAs modulate iPS cell generation.
abstract: Although induced pluripotent stem cells (iPSCs) hold great promise for customized regenerative medicine, the molecular basis of reprogramming is largely unknown. Overcoming barriers that maintain cell identities is a critical step in the reprogramming of differentiated cells. Since microRNAs (miRNAs) modulate target genes tissue-specifically, we reasoned that distinct mouse embryonic fibroblast (MEF)-enriched miRNAs post-transcriptionally modulate proteins that function as reprogramming barriers. Inhibiting these miRNAs should influence cell signaling to lower those barriers. Here we show that depleting miR-21 and miR-29a enhances reprogramming efficiency in MEFs. We also show that the p53 and ERK1/2 pathways are regulated by miR-21 and miR-29a and function in reprogramming. In addition, we provide the first evidence that c-Myc enhances reprogramming partly by repressing MEF-enriched miRNAs, such as miR-21 and miR-29a. Our results demonstrate the significance of miRNA function in regulating multiple signaling networks involved in iPSC generation. These studies should facilitate development of clinically applicable reprogramming strategies.
authors.affiliation: Program for RNA Biology, Sanford-Burnham Medical Research Institute, La Jolla, California 92037, USA.
authors.forename: Chao-Shun
authors.initials: CS
authors.lastname: Yang
authors.forename: Zhonghan
authors.initials: Z
authors.lastname: Li
authors.forename: Tariq M
authors.initials: TM
authors.lastname: Rana
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D035683:MicroRNAs; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc