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Nat Biotechnol. 2015 Jul;33(7):769-74. doi: 10.1038/nbt.3270. Epub 2015 Jun 22.

Transient acquisition of pluripotency during somatic cell transdifferentiation with iPSC reprogramming factors.

Author information

1
1] The Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel. [2] The Department of Gastroenterology, Rambam Health Care Campus &Bruce Rappaport School of Medicine, Technion Institute of Technology, Haifa, Israel.
2
The Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
3
Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.
4
1] The Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel. [2] The Department of Pediatrics and the Pediatric Immunology Unit, Rambam Health Care Campus &Bruce Rappaport School of Medicine, Technion Institute of Technology, Haifa, Israel.
5
Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota, USA.

Abstract

Somatic cells can be transdifferentiated to other cell types without passing through a pluripotent state by ectopic expression of appropriate transcription factors. Recent reports have proposed an alternative transdifferentiation method in which fibroblasts are directly converted to various mature somatic cell types by brief expression of the induced pluripotent stem cell (iPSC) reprogramming factors Oct4, Sox2, Klf4 and c-Myc (OSKM) followed by cell expansion in media that promote lineage differentiation. Here we test this method using genetic lineage tracing for expression of endogenous Nanog and Oct4 and for X chromosome reactivation, as these events mark acquisition of pluripotency. We show that the vast majority of reprogrammed cardiomyocytes or neural stem cells obtained from mouse fibroblasts by OSKM-induced 'transdifferentiation' pass through a transient pluripotent state, and that their derivation is molecularly coupled to iPSC formation mechanisms. Our findings underscore the importance of defining trajectories during cell reprogramming by various methods.

Comment in

PMID:
26098448
PMCID:
PMC4500825
DOI:
10.1038/nbt.3270
[Indexed for MEDLINE]
Free PMC Article

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