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Stem Cell Reports. 2015 Jun 9;4(6):1125-39. doi: 10.1016/j.stemcr.2015.04.009. Epub 2015 May 21.

Transcriptome Signature and Regulation in Human Somatic Cell Reprogramming.

Author information

1
Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06520, USA.
2
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.
3
Department of Cell Biology, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06520, USA.
4
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.
5
Cancer Research Laboratory, LKS Flow Cytometry Facility, University of California, Berkeley, Berkeley, CA 94720, USA.
6
Department of Genetics, Stanford University, Stanford, CA 94305, USA.
7
Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address: inhyun.park@yale.edu.

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.

PMID:
26004630
PMCID:
PMC4471828
DOI:
10.1016/j.stemcr.2015.04.009
[Indexed for MEDLINE]
Free PMC Article

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