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Nuclear reprogramming in heterokaryons is rapid, extensive, and bidirectional
Author(s) -
Palermo Adam,
Doyonnas Regis,
Bhutani Nidhi,
Pomerantz Jason,
Alkan Ozan,
Blau Helen M.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.08-122903
Subject(s) - reprogramming , heterokaryon , cell fusion , microbiology and biotechnology , transcriptome , biology , phenotype , cell , gene , gene expression , genetics , mutant
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. FASEB J . 23, 1431–1440 (2009)