Article abstract
Nature Cell Biology 5, 959 - 966 (2003)
Published online: 15 October 2003 | doi:10.1038/ncb1053
Stable reprogrammed heterokaryons form spontaneously in Purkinje neurons after bone marrow transplant
James M. Weimann1, Clas B. Johansson1, Angelica Trejo1 & Helen M. Blau1
Abstract
Heterokaryons are the product of cell fusion without subsequent nuclear or chromosome loss. Decades of research using Sendai-virus or polyethylene glycol (PEG)-mediated fusion in tissue culture showed that the terminally differentiated state of a cell could be altered. But whether stable non-dividing heterokaryons could occur in animals has remained unclear. Here, we show that green fluorescent protein (GFP)-positive bone-marrow-derived cells (BMDCs) contribute to adult mouse Purkinje neurons through cell fusion. The formation of heterokaryons increases in a linear manner over 1.5 years and seems to be stable. The dominant Purkinje neurons caused the BMDC nuclei within the resulting heterokaryons to enlarge, exhibit dispersed chromatin and activate a Purkinje neuron-specific transgene, L7-GFP. The observed reprogrammed heterokaryons that form in brain may provide insights into gene regulation associated with cell-fate plasticity.
- Baxter Laboratory in Genetic Pharmacology, Department of Microbiology and Immunology, Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Correspondence to: James M. Weimann1 e-mail: jweimann@stanford.edu
Correspondence to: Helen M. Blau1 e-mail: hblau@stanford.edu
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