Genome-wide characterization of the routes to pluripotency
| Autor: | Hussein, Samer M I, Puri, Mira C, Tonge, Peter D, Benevento, Marco, Corso, Andrew J, Clancy, Jennifer L, Mosbergen, Rowland, Li, Mira, Lee, Dong-Sung, Cloonan, Nicole, Wood, David L A, Munoz, Javier, Middleton, Robert, Korn, Othmar, Patel, Hardip R, White, Carl A, Shin, Jong-Yeon, Gauthier, Maely E, Lê Cao, Kim-Anh, Kim, Jong-Il, Mar, Jessica C, Shakiba, Nika, Ritchie, William, Rasko, John E J, Grimmond, Sean M, Zandstra, Peter W, Wells, Christine A, Preiss, Thomas, Seo, Jeong-Sun, Heck, Albert J R, Rogers, Ian M, Nagy, Andras, Sub Biomol.Mass Spectrometry & Proteom., Sub Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics, Molecular Pharmacy |
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| Přispěvatelé: | Sub Biomol.Mass Spectrometry & Proteom., Sub Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics, Molecular Pharmacy |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Proteomics
Proteome Transcription Genetic Induced Pluripotent Stem Cells Computational biology Histones Mice Animals Transgenes Epigenetics Induced pluripotent stem cell Embryonic Stem Cells Epigenomics Genetics Internet Genome Multidisciplinary biology Epistasis Genetic DNA Methylation Fibroblasts Cellular Reprogramming Chromatin Assembly and Disassembly Embryonic stem cell Chromatin Histone DNA methylation biology.protein RNA Long Noncoding Transcriptome Reprogramming Transcription Factors |
| Zdroj: | Nature, 516(7530), 198. Nature Research Nature |
| ISSN: | 0028-0836 |
| Popis: | Somatic cell reprogramming to a pluripotent state continues to challenge many of our assumptions about cellular specification, and despite major efforts, we lack a complete molecular characterization of the reprograming process. To address this gap in knowledge, we generated extensive transcriptomic, epigenomic and proteomic data sets describing the reprogramming routes leading from mouse embryonic fibroblasts to induced pluripotency. Through integrative analysis, we reveal that cells transition through distinct gene expression and epigenetic signatures and bifurcate towards reprogramming transgene-dependent and -independent stable pluripotent states. Early transcriptional events, driven by high levels of reprogramming transcription factor expression, are associated with widespread loss of histone H3 lysine 27 (H3K27me3) trimethylation, representing a general opening of the chromatin state. Maintenance of high transgene levels leads to re-acquisition of H3K27me3 and a stable pluripotent state that is alternative to the embryonic stem cell (ESC)-like fate. Lowering transgene levels at an intermediate phase, however, guides the process to the acquisition of ESC-like chromatin and DNA methylation signature. Our data provide a comprehensive molecular description of the reprogramming routes and is accessible through the Project Grandiose portal at http://www.stemformatics.org. |
| Databáze: | OpenAIRE |
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