Transcriptome Signature and Regulation in Human Somatic Cell Reprogramming

Yoshiaki Tanaka; Eriona Hysolli; Juan Su; Yangfei Xiang; Kun-Yong Kim; Mei Zhong; Yumei Li; Kartoosh Heydari; Ghia Euskirchen; Michael P Snyder; Xinghua Pan; Sherman Morton Weissman; In-Hyun Park

doi:10.1016/j.stemcr.2015.04.009

Transcriptome Signature and Regulation in Human Somatic Cell Reprogramming

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

Authors

Affiliations

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: [email protected].

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Alternative Splicing
Animals
Base Sequence
Cellular Reprogramming*
Cyclin E / genetics
Cyclin E / metabolism
Embryonic Stem Cells / cytology
Embryonic Stem Cells / metabolism
Gene Expression Regulation
Humans
Induced Pluripotent Stem Cells / cytology
Induced Pluripotent Stem Cells / metabolism*
Kruppel-Like Factor 4
Kruppel-Like Transcription Factors / genetics
Kruppel-Like Transcription Factors / metabolism
Mice
Molecular Sequence Data
Octamer Transcription Factor-3 / genetics
Octamer Transcription Factor-3 / metabolism
Oncogene Proteins / genetics
Oncogene Proteins / metabolism
Polymorphism, Single Nucleotide
Principal Component Analysis
Proto-Oncogene Proteins c-myc / genetics
Proto-Oncogene Proteins c-myc / metabolism
RNA / chemistry
SOXB1 Transcription Factors / genetics
SOXB1 Transcription Factors / metabolism
Sequence Analysis, RNA
Transcriptome*

Substances

CCNE1 protein, human
Cyclin E
KLF4 protein, human
Klf4 protein, mouse
Kruppel-Like Factor 4
Kruppel-Like Transcription Factors
Octamer Transcription Factor-3
Oncogene Proteins
Proto-Oncogene Proteins c-myc
SOXB1 Transcription Factors
RNA

Associated data

GENBANK/KR134287
GEO/GSE67915

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding