title: Transcriptome Signature and Regulation in Human Somatic Cell Reprogramming.
abstract: Reprogramming of somatic cells produces induced pluripotent stem cells (iPSCs) that are invaluable resources for biomedical research. Here, we extended the previous transcriptome studies by performing RNA-seq on cells defined by a combination of multiple cellular surface markers. We found that transcriptome changes during early reprogramming occur independently from the opening of closed chromatin by OCT4, SOX2, KLF4, and MYC (OSKM). Furthermore, our data identify multiple spliced forms of genes uniquely expressed at each progressive stage of reprogramming. In particular, we found a pluripotency-specific spliced form of CCNE1 that is specific to human and significantly enhances reprogramming. In addition, single nucleotide polymorphism (SNP) expression analysis reveals that monoallelic gene expression is induced in the intermediate stages of reprogramming, while biallelic expression is recovered upon completion of reprogramming. Our transcriptome data provide unique opportunities in understanding human iPSC reprogramming.
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Eriona
authors.initials: E
authors.lastname: Hysolli
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06520, USA; Department of Cell Biology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Yangfei
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Kun-Yong
authors.initials: KY
authors.lastname: Kim
authors.affiliation: Department of Cell Biology, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhong
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06520, USA; Department of Dermatology, Jiangsu University Affiliated Hospital, Zhenjiang 212000, PRC.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Cancer Research Laboratory, LKS Flow Cytometry Facility, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Kartoosh
authors.initials: K
authors.lastname: Heydari
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Ghia
authors.initials: G
authors.lastname: Euskirchen
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Snyder
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Xinghua
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Sherman Morton
authors.initials: SM
authors.lastname: Weissman
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address: inhyun.park@yale.edu.
authors.forename: In-Hyun
authors.initials: IH
authors.lastname: Park
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D065150:Cellular Reprogramming; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000737:chemistry; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D017423:Sequence Analysis, RNA; D059467:Transcriptome
chemical_list: C475820:CCNE1 protein, human; D019927:Cyclin E; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D050814:Octamer Transcription Factor-3; D015513:Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D055748:SOXB1 Transcription Factors; D012313:RNA