title: Global transcriptional analysis of nuclear reprogramming in the transition from MEFs to iPSCs.
abstract: Induced pluripotent stem cells (iPSCs) are flourishing in the investigation of cell reprogramming. However, we still know little about the sequential molecular mechanism during somatic cell reprogramming (SCR). Here, we first observed rapid generation of colonies whereas mouse embryonic fibroblasts (MEFs) were induced by OCT4, SOX2, KLF4 (OSK), and vitamin C for 7 days. The colony's global transcriptional profiles were analyzed using Affymetrix microarray. Microarray data confirmed that SCR was a process in which transcriptome got reversed and pluripotent genes expressed de novo. There were many changes, especially substantial growth expression of epigenetic factors, on transcriptome during the transition from Day 7 to iPSCs indicating that this period may provide 'flexibility' genome structure, chromatin remodeling, and epigenetic modifications to rebind to the transcriptional factors. Several biological processes such as viral immune response, apoptosis, cell fate specification, and cell communication were mainly involved before Day 7 whereas cell cycle, DNA methylation, and histone modification were mainly involved after Day 7. Furthermore, it was suggested that p53 signaling contributed to the transition 'hyperdynamic plastic' cell state and assembled cell niche for SCR, and small molecular compounds useful for chromatin remodeling can enhance iPSCs by exciting epigenetic modification rather than the exogenous expression of more TFs vectors.
authors.affiliation: Department of Animal Breeding & Genetics, College of Animal Science & Technology, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, China.
authors.forename: Fulu
authors.initials: F
authors.lastname: Dong
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Song
authors.forename: Jinping
authors.initials: J
authors.lastname: Zhang
authors.forename: Youde
authors.initials: Y
authors.lastname: Lu
authors.forename: Chunlei
authors.initials: C
authors.lastname: Song
authors.forename: BaoChun
authors.initials: B
authors.lastname: Jiang
authors.forename: Baole
authors.initials: B
authors.lastname: Zhang
authors.forename: Peiqing
authors.initials: P
authors.lastname: Cong
authors.forename: Hongyan
authors.initials: H
authors.lastname: Sun
authors.forename: Fangxiong
authors.initials: F
authors.lastname: Shi
authors.forename: Honglin
authors.initials: H
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D001205:Ascorbic Acid / Q000378:metabolism; D002450:Cell Communication; D002453:Cell Cycle; D065150:Cellular Reprogramming; D042002:Chromatin Assembly and Disassembly; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D016678:Genome; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D059467:Transcriptome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D016159:Tumor Suppressor Protein p53; D001205:Ascorbic Acid