Letter abstract
Nature Cell Biology 10, 575 - 583 (2008)
Published online: 20 April 2008 | doi:10.1038/ncb1720
Extensive fusion of haematopoietic cells with Purkinje neurons in response to chronic inflammation
Clas B. Johansson1,4, Sawsan Youssef2, Kassie Koleckar1, Colin Holbrook1, Regis Doyonnas1, Stephane Y. Corbel3, Lawrence Steinman2, Fabio M. V. Rossi3 & Helen M. Blau1
Transplanted bone marrow-derived cells (BMDCs) have been reported to fuse with cells of diverse tissues1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, but the extremely low frequency of fusion has led to the view that such events are biologically insignificant. Nonetheless, in mice with a lethal recessive liver disease (tyrosinaemia), transplantation of wild-type BMDCs restored liver function by cell fusion and prevented death3, 9, indicating that cell fusion can have beneficial effects. Here we report that chronic inflammation resulting from severe dermatitis or autoimmune encephalitis leads to robust fusion of BMDCs with Purkinje neurons and formation of hundreds of binucleate heterokaryons per cerebellum, a 10–100-fold higher frequency than previously reported8, 10, 11, 14. Single haematopoietic stem-cell transplants showed that the fusogenic cell is from the haematopoietic lineage and parabiosis experiments revealed that fusion can occur without irradiation. Transplantation of rat bone marrow into mice led to activation of dormant rat Purkinje neuron-specific genes in BMDC nuclei after fusion with mouse Purkinje neurons, consistent with nuclear reprogramming. The precise neurological role of these heterokaryons awaits elucidation, but their frequency in brain after inflammation is clearly much higher than previously appreciated.
- Baxter Laboratory in Genetic Pharmacology, Stanford University School of Medicine, Stanford, CA 94305-5175, USA.
- Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305-5175, USA.
- The Biomedical Research Centre, UBC, Vancouver, BC V6T 1C7, Canada.
- Present address: CMM and Department of Clinical Neuroscience, Karolinska Institutet, SE-171 76, Stockholm, Sweden.
Correspondence to: Clas B. Johansson1,4 e-mail: clas.johansson@ki.se
Correspondence to: Helen M. Blau1 e-mail: hblau2@stanford.edu
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