期刊
STEM CELL REPORTS
卷 4, 期 4, 页码 727-743出版社
CELL PRESS
DOI: 10.1016/j.stemcr.2015.02.004
关键词
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资金
- Cabinet Office, Government of Japan
- Japan Society for the Promotion of Science (JSPS)
- Core Center for iPS Cell Research
- Research Center Network for Realization of Regenerative Medicine
- Japan Science and Technology Agency (JST)
- EPASI (JSPS/National Science Foundation)
- JSPS
As the quintessential reprogramming model, OCT3/4, SOX2, KLF4, and c-MYC re-wire somatic cells to achieve induced pluripotency. Yet, subtle differences in methodology confound comparative studies of reprogramming mechanisms. Employing transposons, we systematically assessed cellular and molecular hallmarks of mouse somatic cell reprogramming by various polycistronic cassettes. Reprogramming responses varied in the extent of initiation and stabilization of transgene-independent pluripotency. Notably, the cassettes employed one of two KLF4 variants, differing only by nine N-terminal amino acids, which generated dissimilar protein stoichiometry. Extending the shorter variant by nine N-terminal amino acids or augmenting stoichiometry by KLF4 supplementation rescued both protein levels and phenotypic disparities, implicating a threshold in determining reprogramming outcomes. Strikingly, global gene expression patterns elicited by published polycistronic cassettes diverged according to each KLF4 variant. Our data expose a Klf4 reference cDNA variation that alters polycistronic factor stoichiometry, predicts reprogramming hallmarks, and guides comparison of compatible public data sets.
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