Two-factor reprogramming of somatic cells to pluripotent stem cells reveals partial functional redundancy of Sox2 and Klf4

Nemajerova, A., Kim, S. Y., Petrenko, O., Moll, U. M. (August 2012) Two-factor reprogramming of somatic cells to pluripotent stem cells reveals partial functional redundancy of Sox2 and Klf4. Cell Death and Differentiation, 19 (8). pp. 1268-1276. ISSN 1350-9047

URL: http://www.ncbi.nlm.nih.gov/pubmed/22539002
DOI: 10.1038/cdd.2012.45

Abstract

Ectopic expression of defined sets of transcription factors in somatic cells enables them to adopt the qualities of pluripotency. Mouse embryonic fibroblasts (MEFs) are the classic target cell used to elucidate the core principles of nuclear reprogramming. However, their phenotypic and functional heterogeneity represents a major hurdle for mechanistic studies aimed at defining the molecular nature of cellular plasticity. We show that reducing the complexity of MEFs by flow cytometry allows the isolation of discrete cell subpopulations that can be efficiently reprogrammed to pluripotency with fewer genes. Using these FACS-sorted cells, we performed a systematic side-by-side analysis of the reprogramming efficiency with different two-and three-factor combinations of Oct4, Sox2 and Klf4. We show that introduction of exogenous Oct4 with either Sox2 or Klf4 does not directly convert MEFs to a pluripotent state. Instead, each combination of factors disrupts the normal cellular homeostasis and establishes transient states characterized by the concurrent expression of mixed lineage markers. These cells convert into induced pluripotent stem cells in a stochastic fashion. Our data suggest that there is a partial functional redundancy between Sox2 and Klf4 in the disruption of cellular homeostasis and activation of regulatory networks that define pluripotency. Cell Death and Differentiation (2012) 19, 1268-1276; doi:10.1038/cdd.2012.45; published online 27 April 2012

Item Type: Paper
Additional Information: ISI Document Delivery No.: 971YO Times Cited: 0 Cited Reference Count: 40 Nemajerova, A. Kim, S. Y. Petrenko, O. Moll, U. M. NYSTEM[N08T-040]; Lymphoma Research Foundation This work was supported by NYSTEM contract no. N08T-040 to UMM and OP. AN was supported by a fellowship from the Lymphoma Research Foundation. Nature publishing group London
Uncontrolled Keywords: somatic cell reprogramming induced pluripotent stem cells iPSC neural stem progenitor cells transgenic mice expression fibroblasts mechanisms mouse oct4
Subjects: therapies > stem cells
CSHL Authors:
Communities: CSHL labs > Mills lab
Depositing User: Matt Covey
Date: August 2012
Date Deposited: 30 Jan 2013 16:52
Last Modified: 30 Jan 2013 16:52
PMCID: PMC3392633
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27012

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