Stable reprogrammed heterokaryons form spontaneously in Purkinje neurons after bone marrow transplant.
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.
Weimann
James M
JM
Baxter Laboratory in Genetic Pharmacology, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. jweimann@stanford.edu
Johansson
Clas B
CB
Trejo
Angelica
A
Blau
Helen M
HM
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002459:Cell Fusion; D002843:Chromatin / Q000378:metabolism; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins; D017404:In Situ Hybridization, Fluorescence; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011689:Purkinje Cells / Q000648:ultrastructure*; D019076:Transgenes
D002843:Chromatin; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins