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          Institute: MPI für molekulare Biomedizin     Collection: Yearbook 2013     Display Documents

ID: 648330.0, MPI für molekulare Biomedizin / Yearbook 2013
Zfp296 is a novel, pluripotent-specific reprogramming factor
Authors:Fischedick, G.; Klein, D. C.; Wu, G.; Esch, D.; Hoing, S.; Han, D. W.; Reinhardt, P.; Hergarten, K.; Tapia, N.; Scholer, H. R.; Sterneckert, J. L.
Date of Publication (YYYY-MM-DD):2012
Title of Journal:PLoS ONE
Issue / Number:4
Start Page:e34645
Review Status:Internal review
Audience:Not Specified
Abstract / Description:Expression of the four transcription factors Oct4, Sox2, Klf4, and c-Myc (OSKM) is sufficient to reprogram somatic cells into induced pluripotent stem (iPSCs). However, this process is slow and inefficient compared with the fusion of somatic cells with embryonic stem cells (ESCs), indicating that ESCs express additional factors that can enhance the efficiency of reprogramming. We had previously developed a method to detect and isolate early neural induction intermediates during the differentiation of mouse ESCs. Using the gene expression profiles of these intermediates, we identified 23 ESC-specific transcripts and tested each for the ability to enhance iPSC formation. Of the tested factors, zinc finger protein 296 (Zfp296) led to the largest increase in mouse iPSC formation. We confirmed that Zfp296 was specifically expressed in pluripotent stem cells and germ cells. Zfp296 in combination with OSKM induced iPSC formation earlier and more efficiently than OSKM alone. Through mouse chimera and teratoma formation, we demonstrated that the resultant iPSCs were pluripotent. We showed that Zfp296 activates transcription of the Oct4 gene via the germ cell-specific conserved region 4 (CR4), and when overexpressed in mouse ESCs leads to upregulation of Nanog expression and downregulation of the expression of differentiation markers, including Sox17, Eomes, and T, which is consistent with the observation that Zfp296 enhances the efficiency of reprogramming. In contrast, knockdown of Zfp296 in ESCs leads to the expression of differentiation markers. Finally, we demonstrated that expression of Zfp296 in ESCs inhibits, but does not block, differentiation into neural cells.
Free Keywords:Animals; Antigens, Differentiation/metabolism; Cell Dedifferentiation; Cell Differentiation; Chimera; DNA Methylation; DNA-Binding Proteins/genetics/metabolism/*physiology; Embryonic Stem Cells/metabolism; Female; Gene Expression; HEK293 Cells; Humans; Induced Pluripotent Stem Cells/*physiology/transplantation; Male; Mice; Mice, Inbred C57BL; Mice, SCID; Octamer Transcription Factor-3/genetics; Organ Specificity; Promoter Regions, Genetic; Teratoma/pathology; Transcription Factors/genetics/physiology
External Publication Status:published
Document Type:Article
Communicated by:keuker
Affiliations:MPI für molekulare Biomedizin
External Affiliations:%G eng
Identifiers:ISSN:1932-6203 (Electronic) 1932-6203 (Linking) %R 10.1... [ID No:1]
URL:http://www.ncbi.nlm.nih.gov/pubmed/22485183 [ID No:2]
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