Transplanted bone marrow regenerates liver by cell fusion
Transplanted bone marrow regenerates liver by cell fusion
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DOI：
10.1038/nature01539
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发表时间：
2003-04-24
期刊：
影响因子：
64.8
通讯作者：
Russell, DW
中科院分区：
文献类型：
--
作者：
Vassilopoulos, G;Wang, PR;Russell, DW
几个实验系统的结果表明，一种组织类型的细胞在移植后可以形成其他组织类型。这可能是由于供体组织中存在多潜能或几种类型的成体干细胞，或者是由于供体细胞和受体细胞的融合。在I型酪氨酸血症模型中，富马酸乙酰乙酸酯水解酶基因突变(Fah(-/-))的小鼠在移植Fah(+/+)骨髓细胞后恢复正常肝功能，并形成组织学正常表达Fah(1)的再生肝结节。在这里，我们发现这些肝结节比野生型Fah等位基因含有更多的突变，并且它们的肝细胞同时表达供体和宿主基因，这与宿主细胞和供体细胞融合形成的多倍体基因组一致。用整合了表达绿色荧光蛋白的泡沫病毒载体标记的骨髓细胞，我们鉴定了肝结节和造血细胞中常见的前病毒连接。我们还表明，细胞融合后，造血供体基因组采用了更具肝细胞特异性的表达谱，因为野生型Fah基因被激活，泛造血CD45标记不再表达。
Results from several experimental systems suggest that cells from one tissue type can form other tissue types after transplantation. This could be due to the presence of multipotential or several types of adult stem cells in donor tissues, or alternatively, to fusion of donor and recipient cells. In a model of tyrosinaemia type I, mice with mutations in the fumarylacetoacetate hydrolase gene (Fah(-/-)) regain normal liver function after transplantation of Fah(+/+) bone marrow cells, and form regenerating liver nodules with normal histology that express Fah(1). Here we show that these hepatic nodules contain more mutant than wild-type Fah alleles, and that their hepatocytes express both donor and host genes, consistent with polyploid genome formation by fusion of host and donor cells. Using bone marrow cells marked with integrated foamy virus vectors that express green fluorescent protein, we identify common proviral junctions in hepatic nodules and haematopoietic cells. We also show that the haematopoietic donor genome adopts a more hepatocyte-specific expression profile after cell fusion, as the wild-type Fah gene was activated and the pan-haematopoietic CD45 marker was no longer expressed.