Characterization of immune-matched hematopoietic transplantation in zebrafish
Characterization of immune-matched hematopoietic transplantation in zebrafish
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DOI：
10.1182/blood-2010-09-307488
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发表时间：
2011-04-21
期刊：
影响因子：
20.3
通讯作者：
Zon, Leonard I.
中科院分区：
文献类型：
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作者：
de Jong, Jill L. O.;Burns, Caroline Erter;Zon, Leonard I.
在体内评估造血干细胞(HSC)的功能需要长期的移植试验。虽然斑马鱼是一个发现造血遗传学的强大模型，但造血移植方法一直不发达。在这里，我们建立了一种成年斑马鱼的长期重建试验。移植后3个月，原发和继发受者均出现多系植入。限制稀释数据表明，在65,000个斑马鱼骨髓细胞中，至少有1个细胞具有再繁殖活性，这与哺乳动物的HSC频率一致。我们在19号染色体上的主要组织相容性复合体基因座上定义了斑马鱼的单倍型，并通过造血移植测试了其功能意义。与配对的鱼类相比，配对的供体和受者显著增加了植入率和供体嵌合率。这些数据构成了斑马鱼组织相容性基因的第一次功能测试，使匹配的造血移植得以发展。这为用突变的斑马鱼HSCs和化学物质进行竞争性移植实验奠定了基础，以测试对植入的影响，从而为人类造血疾病和治疗提供了一个以前没有的模型。(血。2011；117(16)：4234-4242)
Evaluating hematopoietic stem cell (HSC) function in vivo requires a long-term transplantation assay. Although zebrafish are a powerful model for discovering the genetics of hematopoiesis, hematopoietic transplantation approaches have been underdeveloped. Here we established a long-term reconstitution assay in adult zebrafish. Primary and secondary recipients showed multilineage engraftment at 3 months after transplantation. Limiting dilution data suggest that at least 1 in 65 000 zebrafish marrow cells contain re-populating activity, consistent with mammalian HSC frequencies. We defined zebrafish haplotypes at the proposed major histocompatibility complex locus on chromosome 19 and tested functional significance through hematopoietic transplantation. Matching donors and recipients dramatically increased engraftment and percentage donor chimerism compared with unmatched fish. These data constitute the first functional test of zebrafish histocompatibility genes, enabling the development of matched hematopoietic transplantations. This lays the foundation for competitive transplantation experiments with mutant zebrafish HSCs and chemicals to test for effects on engraftment, thereby providing a model for human hematopoietic diseases and treatments not previously available. (Blood. 2011;117(16):4234-4242)