title: Nuclear transcriptome profiling of induced pluripotent stem cells and embryonic stem cells identify non-coding loci resistant to reprogramming.
abstract: Identification of functionally relevant differences between induced pluripotent stem cells (iPSC) and reference embryonic stem cells (ESC) remains a central question for therapeutic applications. Differences in gene expression between iPSC and ESC have been examined by microarray and more recently with RNA-SEQ technologies. We here report an in depth analyses of nuclear and cytoplasmic transcriptomes, using the CAGE (cap analysis of gene expression) technology, for 5 iPSC clones derived from mouse lymphocytes B and 3 ESC lines. This approach reveals nuclear transcriptomes significantly more complex in ESC than in iPSC. Hundreds of yet not annotated putative non-coding RNAs and enhancer-associated transcripts specifically transcribed in ESC have been detected and supported with epigenetic and chromatin-chromatin interactions data. We identified super-enhancers transcriptionally active specifically in ESC and associated with genes implicated in the maintenance of pluripotency. Similarly, we detected non-coding transcripts of yet unknown function being regulated by ESC specific super-enhancers. Taken together, these results demonstrate that current protocols of iPSC reprogramming do not trigger activation of numerous cis-regulatory regions. It thus reinforces the need for already suggested deeper monitoring of the non-coding transcriptome when characterizing iPSC clones. Such differences in regulatory transcript expression may indeed impact their potential for clinical applications.
authors: a Division of Genomic Technologies ; RIKEN Center for Life Science Technologies ; Yokohama , Japan.
authors: Alexandre
authors: A
authors: Fort
authors: Daisuke
authors: D
authors: Yamada
authors: Kosuke
authors: K
authors: Hashimoto
authors: Haruhiko
authors: H
authors: Koseki
authors: Piero
authors: P
authors: Carninci
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000235:genetics; D016000:Cluster Analysis; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D020869:Gene Expression Profiling; D056426:Genetic Loci; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D022661:RNA, Untranslated / Q000378:metabolism; D059467:Transcriptome
chemical_list: D018941:Antigens, CD19; D022661:RNA, Untranslated
keywords: CAGE, cap analysis of gene expression; ENCODE, Encyclopedia of DNA Elements; ESC, embryonic stem cells; NAST, Non-Annotated Stem Transcripts; Stem cells; eRNA, enhancer RNA; iPS; iPSC, induced pluripotent stem cells; lncRNA long non-coding RNA; lncRNAs; ncRNA, non-coding RNA; non-coding RNA; pluripotency; super-enhancers; transcriptome