Embryonic Stem Cells Induce Pluripotency in Somatic Cell Fusion through Biphasic Reprogramming

It is a long-held paradigm that cell fusion reprograms gene expression but the extent of reprogramming and whether it is affected by the cell types employed remain unknown. We recently showed that the silencing of somatic genes is attributable to either trans-acting cellular environment or cis-actin...

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Bibliographic Details
Published in:Molecular cell 2012-04, Vol.46 (2), p.159-170
Main Authors: Foshay, Kara M., Looney, Timothy J., Chari, Sheila, Mao, Frank Fuxiang, Lee, Jae Hyun, Zhang, Li, Fernandes, Croydon J., Baker, Samuel W., Clift, Kayla L., Gaetz, Jedidiah, Di, Chun-Guang, Xiang, Andy Peng, Lahn, Bruce T.
Format: Article
Language:English
Subjects:
Animals
Cell Differentiation
Cell Fusion
Chromatin
DNA biosynthesis
DNA Replication
Embryo cells
embryonic stem cells
Embryonic Stem Cells - cytology
Gene expression
Gene Silencing
genes
Genomes
Kinetics
Mice
Oct-4 protein
Pluripotent Stem Cells - cytology
Replication
Somatic cells
Stem cells
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Summary:It is a long-held paradigm that cell fusion reprograms gene expression but the extent of reprogramming and whether it is affected by the cell types employed remain unknown. We recently showed that the silencing of somatic genes is attributable to either trans-acting cellular environment or cis-acting chromatin context. Here, we examine how trans- versus cis-silenced genes in a somatic cell type behave in fusions to another somatic cell type or to embryonic stem cells (ESCs). We demonstrate that while reprogramming of trans-silenced somatic genes occurs in both cases, reprogramming of cis-silenced somatic genes occurs only in somatic-ESC fusions. Importantly, ESCs reprogram the somatic genome in two distinct phases: trans-reprogramming occurs rapidly, independent of DNA replication, whereas cis-reprogramming occurs with slow kinetics requiring DNA replication. We also show that pluripotency genes Oct4 and Nanog are cis-silenced in somatic cells. We conclude that cis-reprogramming capacity is a fundamental feature distinguishing ESCs from somatic cells. [Display omitted] ► Reprogramming of the somatic genome in somatic-ESC fusions is a biphasic process ► The ability to erase cis-silencing is a unique property of ESCs ► Oct4 and Nanog are cis-silenced in somatic cells ► Cis-reprogramming by ESCs requires DNA replication, but not Aid expression
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2012.02.013