Cell fusion is the principal source of bone-marrow-derived hepatocytes
Cell fusion is the principal source of bone-marrow-derived hepatocytes
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DOI：
10.1038/nature01531
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发表时间：
2003-04-24
期刊：
影响因子：
64.8
通讯作者：
Grompe, M
中科院分区：
文献类型：
--
作者：
Wang, X;Willenbring, H;Grompe, M
有证据表明，造血干细胞可能具有意想不到的发育可塑性，突出了治疗潜力。例如，骨髓来源的肝细胞可以重建富马酰乙酰乙酸水解酶缺乏症小鼠的肝脏，并纠正其肝脏疾病（1）。为了确定这种小鼠模型的潜在机制，我们进行了骨髓源性肝细胞的连续移植。在这里，我们通过Southern印迹分析表明，与原始纯合供体细胞相比，肝脏中的再生肝细胞对于供体骨髓特有的等位基因是杂合的。此外，从雌性供体小鼠移植到雄性受体的肝细胞的细胞遗传学分析证明了80，XXXY（二倍体到二倍体融合）和120，XXXXYY（二倍体到四倍体融合）核型，表明供体和宿主细胞之间的融合。我们的结论是骨髓来源的肝细胞来自细胞融合，而不是造血干细胞的分化。
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 disease(1). 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.