Generation of neural progenitors from induced Bama miniature pig pluripotent cells
Generation of neural progenitors from induced Bama miniature pig pluripotent cells
复制标题
诱导巴马小型猪多能细胞产生神经祖细胞。
DOI：
10.1530/rep-13-0196
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发表时间：
2014-01-01
期刊：
影响因子：
3.8
通讯作者：
Lei, Lei
中科院分区：
文献类型：
--
作者：
Li, Xue;Shan, Zhi-Yan;Lei, Lei
猪多能细胞可能代表用于开发人类生物医学领域中的治疗应用的有利实验工具。然而，以前已经证明很难从早期胚胎中建立，并且其多能性尚未明确记录。近年来，诱导多能干细胞（induced pluripotent stem，iPS）技术提供了一种将体细胞重编程为多能状态的新方法。与或不与某些小分子一起产生iPS细胞已成为常规技术。然而，使用病毒感染与小分子一起从猪胚胎组织产生iPS细胞尚未报道。在这里，我们报告了使用iPS技术与丙戊酸（VPA）组合诱导猪多能细胞（iPPC）的产生。VPA处理显著增加了多能基因的表达，并在早期重编程中发挥重要作用。我们发现iPPC在形态和多能标记（例如OCT 4、NANOG和SSEA 1）方面与猪外胚细胞相似。其核型正常，在离体培养条件下可形成胚状体，并表达三种胚层标记。此外，iPPCs经维甲酸和细胞外基质诱导后可直接分化为神经前体细胞。本研究建立了一种合理的猪多能干细胞的制备方法，为人类神经系统疾病的治疗提供了新的供体细胞来源。
Pig pluripotent cells may represent an advantageous experimental tool for developing therapeutic application in the human biomedical field. However, it has previously been proven to be difficult to establish from the early embryo and its pluripotency has not been distinctly documented. In recent years, induced pluripotent stem (iPS) cell technology provides a new method of reprogramming somatic cells to pluripotent state. The generation of iPS cells together with or without certain small molecules has become a routine technique. However, the generation of iPS cells from pig embryonic tissues using viral infections together with small molecules has not been reported. Here, we reported the generation of induced pig pluripotent cells (iPPCs) using the iPS technology in combination with valproic acid (VPA). VPA treatment significantly increased the expression of pluripotent genes and played an important role in early reprogramming. We showed that iPPCs resembled pig epiblast cells in their morphology and pluripotent markers, such as OCT4, NANOG, and SSEA1. It had a normal karyotype and could form embryoid bodies, which express three germ layer markers in vitro. In addition, the iPPCs might directly differentiate into neural progenitors after being induced with the retinoic acid and extracellular matrix. Our study established a reasonable method to generate pig pluripotent cells, which might be a new donor cell source for human neural disease therapy.