Cell fusion is the principal source of bone-marrow-derived hepatocytes

Xin Wang, Holger Willenbring, Yassmine Akkari, Yumi Torimaru, Mark Foster, Muhsen Al-Dhalimy, Eric Lagasse, Milton Finegold, Susan Olson, Markus Grompe

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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.

Original languageEnglish (US)
Pages (from-to)897-901
Number of pages5
JournalNature
Volume422
Issue number6934
DOIs
StatePublished - Apr 24 2003

ASJC Scopus subject areas

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    Wang, X., Willenbring, H., Akkari, Y., Torimaru, Y., Foster, M., Al-Dhalimy, M., Lagasse, E., Finegold, M., Olson, S., & Grompe, M. (2003). Cell fusion is the principal source of bone-marrow-derived hepatocytes. Nature, 422(6934), 897-901. https://doi.org/10.1038/nature01531