Induced Pluripotent Stem Cells from Pigs and Other Ungulate Species: An Alternative to Embryonic Stem Cells?
Induced Pluripotent Stem Cells from Pigs and Other Ungulate Species: An Alternative to Embryonic Stem Cells?
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DOI：
10.1111/j.1439-0531.2012.02061.x
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发表时间：
2012-08-01
影响因子：
1.7
通讯作者：
Roberts, R. M.
中科院分区：
文献类型：
--
作者：
Ezashi, T.;Telugu, B. P. V. L.;Roberts, R. M.
来自家畜物种的健壮的胚胎干细胞（ESC）系一直难以获得和维持，并且与小鼠ESC不同，没有有助于我们理解体外定向分化的能力。这些细胞也没有提供比原核注射更简单的方法来操纵农业上重要物种的基因组，如牛，羊和猪。诱导多能干细胞（iPSC）通过用一组干细胞基因（最常见但不排他地是POU5F1、SOX 2、KLF4和c-MYC）重编程体细胞（如成纤维细胞）而产生，在这些方面提供了ESC的替代方案，因为它们表现出与ESC相似的多能表型，但易于在实验室中产生。因此，这种细胞与克隆技术相结合，可能有助于将复杂的遗传变化引入牲畜，尽管这种潜力尚未得到证实。猪iPSC可能特别有价值，因为猪是组织移植的主要生物医学模型。一般而言，来自家畜的iPSC与来自人类的iPSC一样，是外胚层类型的，并且依赖于FGF 2和激活素/节点信号传导系统来维持其多能性和生长。最近的实验，其中在存在特异性蛋白激酶抑制剂的情况下在基于LIF的培养基上选择新重编程的猪和牛细胞，已经允许分离幼稚型的iPSC细胞，类似于更顺从的胚泡衍生的小鼠ESC和iPSC。然而，如果这些细胞要实现其生物技术的承诺，仍然存在障碍。
Robust embryonic stem cell (ESC) lines from livestock species have been difficult to derive and maintain, and unlike mouse ESC, have not contributed to our ability to understand directed differentiation in vitro. Nor have such cells yet provided a simpler means than pronuclear injection to manipulate the genomes of agriculturally important species, such as cattle, sheep and pigs. Induced pluripotent stem cells (iPSC) generated by reprogramming somatic cells, such as fibroblasts, with a set of stemness genes, most usually but not exclusively POU5F1, SOX2, KLF4 and c-MYC, offer an alternative to ESC in these regards, as they exhibit a pluripotent phenotype resembling that of ESC, yet are readily generated in the laboratory. Accordingly, such cells, in association with cloning technologies, may be useful for introducing complex genetic changes into livestock, although this potential has yet to be demonstrated. Porcine iPSC may be especially valuable because the pig is a prime biomedical model for tissue transplantation. In general, iPSC from livestock, like those from humans, are of the epiblast type and depend upon FGF2 and activin/nodal signalling systems to maintain their pluripotency and growth. Recent experiments, in which newly reprogrammed porcine and bovine cells were selected on a LIF-based medium in presence of specific protein kinase inhibitors, have allowed iPSC cells of the naive type, resembling the more amenable blastocyst - derived mouse ESC and iPSC to be isolated. However, hurdles still remain if such cells are to achieve their biotechnological promise.