HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 2006-0532v1 25/5/1104    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ambrosi, D. J. Articles by Rasmussen, T. P. Search for Related Content PubMed PubMed Citation Articles by Ambrosi, D. J. Articles by Rasmussen, T. P.

EMBRYONIC STEM CELLS: CHARACTERIZATION SERIES

Genome-Wide Reprogramming in Hybrids of Somatic Cells and Embryonic Stem Cells

^aCenter for Regenerative Biology,
^bDepartment of Molecular and Cell Biology,
^dDepartment of Animal Science, University of Connecticut, Storrs, Connecticut, USA;
^cDepartment of Genetics and Developmental Biology, University of Connecticut Medical School, Farmington, Connecticut, USA

Key Words. Fusion • Reprogramming • Stem cells • Genomics

Correspondence: Theodore P. Rasmussen, Ph.D., Center for Regenerative Biology, 1392 Storrs Road, U-4243 University of Connecticut, Storrs, Connecticut 06269-4243, USA. Telephone: (860) 486-8339; Fax: (860) 486-8809; e-mail: theodore.rasmussen{at}uconn.edu

Received August 25, 2006; accepted for publication January 23, 2007.
First published online in STEM CELLS EXPRESS   February 1, 2007.



Recent experiments demonstrate that somatic nuclei can be reprogrammed to a pluripotent state when fused to ESCs. The resulting hybrids are pluripotent as judged by developmental assays, but detailed analyses of the underlying molecular-genetic control of reprogrammed transcription in such hybrids are required to better understand fusion-mediated reprogramming. We produced hybrids of mouse ESCs and fibroblasts that, although nearly tetraploid, exhibit characteristics of normal ESCs, including apparent immortality in culture, ESC-like colony morphology, and pluripotency. Comprehensive analysis of the mouse embryonic fibroblast/ESC hybrid transcriptome revealed global patterns of gene expression reminiscent of ESCs. However, combined analysis of variance and hierarchical clustering analyses revealed at least seven distinct classes of differentially regulated genes in comparisons of hybrids, ESCs, and somatic cells. The largest class includes somatic genes that are silenced in hybrids and ESCs, but a smaller class includes genes that are expressed at nearly equivalent levels in hybrids and ESCs that contain many genes implicated in pluripotency and chromatin function. Reprogrammed genes are distributed throughout the genome. Reprogramming events include both transcriptional silencing and activation of genes residing on chromosomes of somatic origin. Somatic/ESC hybrid cell lines resemble their pre-fusion ESC partners in terms of behavior in culture and pluripotency. However, they contain unique expression profiles that are similar but not identical to normal ESCs. ESC fusion-mediated reprogramming provides a tractable system for the investigation of mechanisms of reprogramming.

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