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          Institute: MPI für molekulare Biomedizin     Collection: Jahrbuch 2017 (publ. 2016, arch)     Display Documents



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ID: 732154.0, MPI für molekulare Biomedizin / Jahrbuch 2017 (publ. 2016, arch)
MicroRNA-29 impairs the early phase of reprogramming process by targeting active DNA demethylation enzymes and Wnt signaling
Authors:Fraguas, M. S.; Eggenschwiler, R.; Hoepfner, J.; Schiavinato, J. L.; Haddad, R.; Oliveira, L. H.; Araujo, A. G.; Zago, M. A.; Panepucci, R. A.; Cantz, T.
Date of Publication (YYYY-MM-DD):2016-12-19
Title of Journal:Stem Cell Res
Volume:19
Start Page:21
End Page:30
Review Status:Internal review
Audience:Not Specified
Abstract / Description:Somatic cell reprogramming by transcription factors and other modifiers such as microRNAs has opened broad avenues for the study of developmental processes, cell fate determination, and interplay of molecular mechanisms in signaling pathways. However, many of the mechanisms that drive nuclear reprogramming itself remain yet to be elucidated. Here, we analyzed the role of miR-29 during reprogramming in more detail. Therefore, we evaluated miR-29 expression during reprogramming of fibroblasts transduced with lentiviral OKS and OKSM vectors and we show that addition of c-MYC to the reprogramming factor cocktail decreases miR-29 expression levels. Moreover, we found that transfection of pre-miR-29a strongly decreased OKS-induced formation of GFP+-colonies in MEF-cells from Oct4-eGFP reporter mouse, whereas anti-miR-29a showed the opposite effect. Furthermore, we studied components of two pathways which are important for reprogramming and which involve miR-29 targets: active DNA-demethylation and Wnt-signaling. We show that inhibition of Tet1, Tet2 and Tet3 as well as activation of Wnt-signaling leads to decreased reprogramming efficiency. Moreover, transfection of pre-miR-29 resulted in elevated expression of beta-Catenin transcriptional target sFRP2 and increased TCF/LEF-promoter activity. Finally, we report that Gsk3-beta is a direct target of miR-29 in MEF-cells. Together, our findings contribute to the understanding of the molecular mechanisms by which miR-29 influences reprogramming.
Free Keywords:Cellular reprogramming; Ten-eleven translocated 1 (TET1) gene; WNT signaling; miR-29
External Publication Status:published
Document Type:Article
Communicated by:Jeanine Müller-Keuker
Affiliations:MPI für molekulare Biomedizin
External Affiliations:Translational Hepatology and Stem Cell Biology, REBIRTH Cluster of Excellence and Dept. of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany. Electronic address: eggenschwiler.reto@mh-hannover.de. Translational Hepatology and Stem Cell Biology, REBIRTH Cluster of Excellence and Dept. of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany. Electronic address: hoepfner.jeannine@mh-hannover.de. National Institute of Science and Technology in Stem Cell and Cell Therapy (INCTC), Center for Cell Therapy (CTC), Regional Blood Center, Ribeirao Preto, Brazil. Electronic address: josililian@usp.br. University of Brasilia - DF (UNB), Brazil. Electronic address: haddad@unb.br. National Institute of Science and Technology in Stem Cell and Cell Therapy (INCTC), Center for Cell Therapy (CTC), Regional Blood Center, Ribeirao Preto, Brazil. Electronic address: luhabib@yahoo.com.br. Department of Clinical Medicine, Faculty of Medicine, University of Sao Paulo (FMRP-USP), Brazil; National Institute of Science and Technology in Stem Cell and Cell Therapy (INCTC), Center for Cell Therapy (CTC), Regional Blood Center, Ribeirao Preto, Brazil. Electronic address: agoesaraujo@usp.br. Department of Clinical Medicine, Faculty of Medicine, University of Sao Paulo (FMRP-USP), Brazil; National Institute of Science and Technology in Stem Cell and Cell Therapy (INCTC), Center for Cell Therapy (CTC), Regional Blood Center, Ribeirao Preto, Brazil. Electronic address: marazago@usp.br. Department of Clinical Medicine, Faculty of Medicine, University of Sao Paulo (FMRP-USP), Brazil; National Institute of Science and Technology in Stem Cell and Cell Therapy (INCTC), Center for Cell Therapy (CTC), Regional Blood Center, Ribeirao Preto, Brazil. Electronic address: rapane@gmail.com. Translational Hepatology and Stem Cell Biology, REBIRTH Cluster of Excellence and Dept. of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany. Electronic address: cantz.tobias@mh-hannover.de.
Identifiers:ISSN:1876-7753 (Electronic) 1873-5061 (Linking) %R 10.1... [ID No:1]
URL:https://www.ncbi.nlm.nih.gov/pubmed/28038351 [ID No:2]
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