Genome-wide characterization of the routes to pluripotency

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., Le 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. and Nagy, Andras (2014) Genome-wide characterization of the routes to pluripotency. Nature, 516 7530: 198-+. doi:10.1038/nature14046


 
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Author 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.
Le 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
Title Genome-wide characterization of the routes to pluripotency
Journal name Nature   Check publisher's open access policy
ISSN 0028-0836
1476-4687
Publication date 2014-12
Sub-type Article (original research)
DOI 10.1038/nature14046
Volume 516
Issue 7530
Start page 198
End page +
Total pages 26
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2015
Language eng
Formatted abstract
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.
Keyword Embryonic Stem-Cells
Differential Expression Analysis
Gene Expression
Noncoding Rnas
Functional Properties
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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