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First published online January 11, 2007
Stem Cells Vol. 25 No. 4 April 2007, pp. 1013 -1020
doi:10.1634/stemcells.2006-0691; www.StemCells.com
© 2007 AlphaMed Press

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STEM CELL GENETICS AND GENOMICS

Erasure of Cellular Memory by Fusion with Pluripotent Cells

Jeong Tae Doa, Dong Wook Hana,b, Luca Gentilea, Ingeborg Sobek-Klockea, Martin Stehlinga, Hoon Taek Leeb, Hans R. Schölera

aDepartment of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany;
bDepartment of Bioscience and Biotechnology, Bio-Organ Research Center, Konkuk University, Gwangjin-Gu, Seoul, South Korea

Key Words. Differentiation • F9 EC cells • Fusion • Oct4Xist • Reprogramming

Correspondence: Hans R. Schöler, Ph.D., Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20 48149 Münster, Germany. Telephone: 49-251-70365-300; Fax: 49-251-70365-399; e-mail: schoeler{at}mpi-muenster.mpg.de

Received October 30, 2006; accepted for publication January 2, 2007.
First published online in STEM CELLS EXPRESS   January 11, 2007.



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 nonneural 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. Whereas 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.

Disclosure of potential conflicts of interest is found at the end of this article.




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