Reprogramming Factor Stoichiometry Influences the Epigenetic State and Biological Properties of Induced Pluripotent Stem Cells
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.; Welstead, G. Grant; Gao, Qing; Jaenisch, Rudolf; ... Show more Show less
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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.
Date issued
2011-12Department
Massachusetts Institute of Technology. Department of Biology; Whitehead Institute for Biomedical ResearchJournal
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
ISSN
19345909