Nuclear reprogramming in heterokaryons is rapid, extensive, and bidirectional

An understanding of nuclear reprogramming is fundamental to the use of cells in regenerative medicine. Due to technological obstacles, the time course and extent of reprogramming of cells following fusion has not been assessed to date. Here, we show that hundreds of genes are activated or repressed...

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Bibliographic Details
Published in:The FASEB journal 2009-05, Vol.23 (5), p.1431-1440
Main Authors: Palermo, Adam, Doyonnas, Regis, Bhutani, Nidhi, Pomerantz, Jason, Alkan, Ozan, Blau, Helen M
Format: Article
Language:English
Subjects:
Animals
balance of regulators
Cell Differentiation
Cell Fusion
Cellular Reprogramming
gene expression
Gene Expression Profiling - methods
Humans
Hybrid Cells - metabolism
Hybrid Cells - physiology
Keratinocytes - physiology
Mice
microarrays
Oligonucleotide Array Sequence Analysis
Research Communications
somatic fate change
time course
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Summary:An understanding of nuclear reprogramming is fundamental to the use of cells in regenerative medicine. Due to technological obstacles, the time course and extent of reprogramming of cells following fusion has not been assessed to date. Here, we show that hundreds of genes are activated or repressed within hours of fusion of human keratinocytes and mouse muscle cells in heterokaryons, and extensive changes are observed within 4 days. This study was made possible by the development of a broadly applicable approach, species-specific transcriptome amplification (SSTA), which enables global resolution of transcripts derived from the nuclei of two species, even when the proportions of species-specific transcripts are highly skewed. Remarkably, either phenotype can be dominant; an excess of primary keratinocytes leads to activation of the keratinocyte program in muscle cells and the converse is true when muscle cells are in excess. We conclude that nuclear reprogramming in heterokaryons is rapid, extensive, bidirectional, and dictated by the balance of regulators contributed by the cell types.--Adam Palermo, Regis Doyonnas, Nidhi Bhutani, Jason Pomerantz, Ozan Alkan, Helen M. Blau. Nuclear reprogramming in heterokaryons is rapid, extensive, and bidirectional.
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.08-122903