Lung-specific nuclear reprogramming is accompanied by heterokaryon formation and Y chromosome loss following bone marrow transplantation and secondary inflammation
Lung-specific nuclear reprogramming is accompanied by heterokaryon formation and Y chromosome loss following bone marrow transplantation and secondary inflammation
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DOI：
10.1096/fj.06-7861com
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发表时间：
2007-08-01
期刊：
影响因子：
4.8
通讯作者：
Krause, Diane S.
中科院分区：
文献类型：
--
作者：
Herzog, Erica L.;Van Arnam, John;Krause, Diane S.
细胞融合是骨髓源性细胞（BMDCs）具有非造血细胞基因表达模式的一种机制。这个过程发生在许多器官移植后损伤，但从来没有发现在肺。我们在肺部炎症的小鼠模型中进行骨髓（BM）移植，以测试移植的BMDC是否通过与患病的肺细胞融合而产生肺特异性基因表达。对缺乏肺特异性表面活性蛋白C（Sp-C）的小鼠进行致死性照射，移植性别不匹配的野生型骨髓，6个月后处死。19/38个受体显示Sp-C mRNA（RT-PCR）和/或蛋白（通过共聚焦显微镜，平均0.95 +/-1.18 Sp-C+细胞/1000个II型肺细胞）。在雌性BM的男性受体中，65%的Sp-C +细胞含有Y染色体，表明它们来自融合。只有28%的Sp-C +细胞在女性受体的男性BMDCs包含Y染色体，这表明72%的Sp-C表达细胞失去了Y染色体。在移植后炎症的情况下，移植的BMDC的肺细胞特异性重编程主要来自异核体形成。这一过程不会逆转由Sp-C缺乏引起的炎症;然而，进一步的研究可能会发现受益于这种方法的表型。
Cell fusion is one mechanism by which bone marrow-derived cells (BMDCs) take on the gene expression pattern of nonhematopoietic cells. This process occurs in a number of organs with posten-graftment injury but has never been found in the lung. We performed bone marrow (BM) transplant in a murine model of lung inflammation to test whether transplanted BMDCs develop lung-specific gene expression by fusing with diseased pneumocytes. Mice lacking the lung-specific protein surfactant protein C (Sp-C) were lethally irradiated, transplanted with sex mismatched wild-type marrow, and sacrificed 6 months later. Nineteen/38 recipients exhibited Sp-C mRNA (RT-PCR) and/or protein (mean 0.95 +/- 1.18 Sp-C+ cells per 1000 type II pneumocytes by confocal microscopy). In male recipients of female BM, 65% of Sp-C + cells contained the Y chromosome, indicating their origin from fusion. Only 28% of Sp-C + cells in female recipients of male BMDCs contained the Y chromosome, suggesting that 72% of Sp-C-expressing cells lost the Y chromosome. In the setting of post-transplant inflammation, pneumocyte-specific reprogramming of transplanted BMDCs predominantly derives from heterokaryon formation. This process does not reverse inflammation caused by Sp-C deficiency; nevertheless, further investigation may identify phenotypes benefiting from such an approach.