Reprogramming Factor Stoichiometry Influences the Epigenetic State and Biological Properties of Induced Pluripotent Stem Cells
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Carey-2011-Reprogramming Factor.pdf
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Author(s)
Carey, Bryce W.
Markoulaki, Styliani
Hanna, Jacob
Faddah, Dina A.
Buganim, Yosef
Kim, Jongpil
Ganz, Kibibi
Steine, Eveline J.
Cassady, John P.
Creyghton, Menno P.
Date Issued
December 2011
Journal
Cell Stem Cell
Publisher
Elsevier
Citation
Carey, Bryce W., Styliani Markoulaki, Jacob H. Hanna, Dina A. Faddah, Yosef Buganim, Jongpil Kim, Kibibi Ganz, et al. “Reprogramming Factor Stoichiometry Influences the Epigenetic State and Biological Properties of Induced Pluripotent Stem Cells.” Cell Stem Cell 9, no. 6 (December 2011): 588–598. © 2011 Elsevier Inc.
Version
Final published version
Abstract
We compared two genetically highly defined transgenic systems to identify parameters affecting reprogramming of somatic cells to a pluripotent state. Our results demonstrate that the level and stoichiometry of reprogramming factors during the reprogramming process strongly influence the resulting pluripotency of iPS cells. High expression of Oct4 and Klf4 combined with lower expression of c-Myc and Sox2 produced iPS cells that efficiently generated “all-iPSC mice” by tetraploid (4n) complementation, maintained normal imprinting at the Dlk1-Dio3 locus, and did not create mice with tumors. Loss of imprinting (LOI) at the Dlk1-Dio3 locus did not strictly correlate with reduced pluripotency though the efficiency of generating “all-iPSC mice” was diminished. Our data indicate that stoichiometry of reprogramming factors can influence epigenetic and biological properties of iPS cells. This concept complicates efforts to define a “generic” epigenetic state of iPSCs and ESCs and should be considered when comparing different iPS and ES cell lines.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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DOI of Published Version
https://doi.org/10.1016/j.stem.2011.11.003
