Stem Cells
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First published online January 11, 2007
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2006-0691v1
25/4/1013    most recent
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Submitted on October 30, 2006
Accepted on January 2, 2007

Stem Cell Genetics and Genomics

Erasure of cellular memory by fusion with pluripotent cells

Jeong Tae Do 1, Dong Wook Han 2, Luca Gentile 1, Ingeborg Sobek-Klocke 1, Martin Stehling 1, Hoon Taek Lee 3, Hans R. Schöler 1*

1 Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany
2 Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany; Department of Bioscience and Biotechnology, Bio-Organ Research Center, Konkuk University, Seoul, South Korea
3 Department of Bioscience and Biotechnology, Bio-Organ Research Center, Konkuk University, Seoul, South Korea

* To whom correspondence should be addressed. E-mail: schoeler{at}mpi-muenster.mpg.de.


  Abstract

Pluripotent cells have been suggested as a prime source to reprogram somatic cells. We used F9 EC cells as a pluripotent partner to reprogram neurosphere cells (NSCs), because they exhibit a non-neural differentiation potential in the presence of retinoic acid. F9-NSC hybrid cells displayed various features of reprogramming, such as reactivation of pluripotency genes, inactivation of tissue-specific genes, and reactivation of the inactive X chromosome. As the hybrid cells undergo differentiation, the pluripotency markers Oct4 and Nanog were downregulated. While neural marker genes were not upregulated, endodermal and mesodermal markers were, suggesting that NSCs lose memory of their neural origin and preferentially differentiate to the lineages corresponding to the F9 program. After fusion, the methylation status in the Xist region was similar to that of F9 EC cells. However, upon differentiation the Xist region failed to resume the methylation patterns of differentiated cells, suggesting that the Xist in F9-NSC hybrids does not easily acquire a differentiated state.

Key Words. differentiation, F9 EC cells, fusion, Oct4, Xist, reprogramming




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