@article{5da409ecf08b40ca9c374dd01f02c662,
title = "Cell fusion is the principal source of bone-marrow-derived hepatocytes",
abstract = "Evidence suggests that haematopoietic stem cells might have unexpected developmental plasticity, highlighting therapeutic potential. For example, bone-marrow-derived hepatocytes can repopulate the liver of mice with fumarylacetoacetate hydrolase deficiency and correct their liver disease1. To determine the underlying mechanism in this murine model, we performed serial transplantation of bone-marrow-derived hepatocytes. Here we show by Southern blot analysis that the repopulating hepatocytes in the liver were heterozygous for alleles unique to the donor marrow, in contrast to the original homozygous donor cells. Furthermore, cytogenetic analysis of hepatocytes transplanted from female donor mice into male recipients demonstrated 80,XXXY (diploid to diploid fusion) and 120,XXXXYY (diploid to tetraploid fusion) karyotypes, indicative of fusion between donor and host cells. We conclude that hepatocytes derived form bone marrow arise from cell fusion and not by differentiation of haematopoietic stem cells.",
author = "Xin Wang and Holger Willenbring and Yassmine Akkari and Yumi Torimaru and Mark Foster and Muhsen Al-Dhalimy and Eric Lagasse and Milton Finegold and Susan Olson and Markus Grompe",
note = "Funding Information: Acknowledgements We thank F. K. Selker and C. B. Matsen for help with computer analyses; T. Wolfe for technical assistance; G. Mannhaupt for providing some accession numbers; and J. Galagan for comments on the manuscript. E.U.S. acknowledges the hospitality of the Bird laboratory when he initiated this project while on sabbatical, and is thankful to D. Macleod, R. Meehan and F. Antequera for their advice. This work was supported by a US Public Health Service grant to E.U.S. from the National Institutes of Health, and a Senior International Fellowship from the Fogarty International Center of the National Institutes of Health. Funding Information: Acknowledgements This work was supported by NIH grants to MG., E.L., Y.A. and S.O. X.W. is supported by the Juvenile Diabetes Foundation and H.W. by the Deutsche Forschungsgemeinschaft.",
year = "2003",
month = apr,
day = "24",
doi = "10.1038/nature01531",
language = "English (US)",
volume = "422",
pages = "897--901",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "6934",
}