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The developmental potential of iPSCs is greatly influenced by the selection of the reprogramming factors

ABSTRACT: Induced pluripotent stem cells (iPSCs) are commonly generated by transduction of Oct4, Sox2, Klf4 and Myc (OSKM) into somatic cells. Though iPSCs are pluripotent, they frequently exhibit high variation in their quality as measured by chimera contribution and tetraploid (4n) complementation. Thus, improving the quality of iPSCs is an indispensable prerequisite for future iPSC-based therapy. Here we show that one major determinant for iPSCs quality is the combination of reprograming factor selected. Ectopic expression of Sall4, Nanog, Esrrb and Lin28 (SNEL) in MEFs efficiently generated high quality iPSCs as compared to other combinations of factors. SNEL-iPSCs produced approximately 5 times more efficiently “all-iPSC” mice compared to OSKM-iPSCs. While differentially methylated regions, transcript number of master regulators, establishment of ESC-specific super enhancers, and global aneuploidy were comparable between the lines, aberrant expression of 1,765 genes, trisomy of chromosome 8 and abnormal H2A.X deposition were frequently observed in poor quality OSK-iPSCs and OSKM-iPSCs. ChIP-Seq for Med1 in reprogrammed and partially reprogrammed mouse embryonic stem cell lines and corresponding controls

ORGANISM(S): Mus musculus  

SUBMITTER: Andrew Xiao  Batool Akhtar-Zaidi   Joseph R Ecker   Yosef Buganim   Malkiel Cohen   Richard A Young   Sovan Sarkar   Matthew D Schultz   Brian J Abraham   Dina Faddah   Rudolf Jaenisch   Linyu Shi   Peter M Lansdorp   Yupeng He   David Porubsky   Heather Hoke   Elisabeth Kulenkampff   Niek van Wiemartschen   Joseph R Nery   Kibibi Ganz   Qing Gao   Tao Wu   Styliana Markoulaki   Johanna Goldmann    

PROVIDER: E-GEOD-59569 | ArrayExpress | 2014-07-30



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