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Nanog promotes transfer of pluripotency after cell fusion.

TitleNanog promotes transfer of pluripotency after cell fusion.
Publication TypeJournal Article
Year of Publication2006
AuthorsSilva J, Chambers I, Pollard SM, Smith A
JournalNature
Volume441
Issue7096
Pagination997-1001
Date Published2006 Jun 22
ISSN1476-4687
KeywordsAnimals, Cell Differentiation, Cell Fusion, Cell Survival, Cells, Cultured, DNA-Binding Proteins, Embryo, Mammalian, Flow Cytometry, Homeodomain Proteins, Hybrid Cells, Mice, Neurons, Octamer Transcription Factor-3, Pluripotent Stem Cells, Transgenes
Abstract

Through cell fusion, embryonic stem (ES) cells can erase the developmental programming of differentiated cell nuclei and impose pluripotency. Molecules that mediate this conversion should be identifiable in ES cells. One candidate is the variant homeodomain protein Nanog, which has the capacity to entrain undifferentiated ES cell propagation. Here we report that in fusions between ES cells and neural stem (NS) cells, increased levels of Nanog stimulate pluripotent gene activation from the somatic cell genome and enable an up to 200-fold increase in the recovery of hybrid colonies, all of which show ES cell characteristics. Nanog also improves hybrid yield when thymocytes or fibroblasts are fused to ES cells; however, fewer colonies are obtained than from ES x NS cell fusions, consistent with a hierarchical susceptibility to reprogramming among somatic cell types. Notably, for NS x ES cell fusions elevated Nanog enables primary hybrids to develop into ES cell colonies with identical frequency to homotypic ES x ES fusion products. This means that in hybrids, increased Nanog is sufficient for the NS cell epigenome to be reset completely to a state of pluripotency. We conclude that Nanog can orchestrate ES cell machinery to instate pluripotency with an efficiency of up to 100% depending on the differentiation status of the somatic cell.

DOI10.1038/nature04914
Alternate JournalNature
PubMed ID16791199
Grant ListG0300058 / / Medical Research Council / United Kingdom
G9806702 / / Medical Research Council / United Kingdom
/ / Wellcome Trust / United Kingdom