Mechanisms that direct reprogramming of differentiated somatic cells to induced pluripotent stem cells (iPSCs), albeit incomplete in understanding, are highly conserved across all mammalian species studied. Equally, proof of principle that iPSCs can be derived from domestic cattle has been reported in several publications. In our efforts to derive and study bovine iPSCs, we encountered inadequacy of methods to generate, sustain, and characterize these cells. Our results suggest that iPSC protocols optimized for mouse and human somatic cells do not effectively translate to bovine somatic cells, which show some refractoriness to reprogramming that also affects sustenance. Moreover, methods that enhance reprogramming efficiency in mouse and human cells had no effect on improving bovine cell reprogramming. Although use of retroviral vectors coding for bovine OCT4, SOX2, KLF4, cMYC, and NANOG appeared to produce consistent iPSC-like cells from both fibroblasts and cells from the Wharton's jelly, these colonies could not be sustained. Use of bovine genes could successfully reprogram both mouse and human cells. These findings indicated either incomplete reprogramming and/or discordant/inadequate culture conditions for bovine pluripotent stem cells. Therefore, additional studies that advance core knowledge of bovine pluripotency are necessary before any anticipated iPSC-driven bovine technologies can be realized.

中文翻译：

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从牛体细胞诱导的多能干细胞的产生表明多能维持的需求未得到满足。

在理解的所有过程中，尽管理解尚不完善，但将分化的体细胞直接重编程为诱导性多能干细胞（iPSC）的机制在所有研究的哺乳动物物种中都高度保守。同样，一些出版物中已经报道了iPSC可以源自家畜的原理性证明。在我们努力衍生和研究牛iPSC的过程中，我们遇到了不足以生成，维持和表征这些细胞的方法。我们的结果表明，针对小鼠和人类体细胞进行优化的iPSC协议不能有效地转化为牛体细胞，这显示出对重编程的抵抗力，这也影响了维持性。此外，增强小鼠和人类细胞中重编程效率的方法对改善牛细胞重编程没有影响。尽管使用编码牛OCT4，SOX2，KLF4，cMYC和NANOG的逆转录病毒载体似乎可以从成纤维细胞和沃顿氏胶冻中产生一致的iPSC样细胞，但这些菌落无法维持。牛基因的使用可以成功地重编程小鼠和人类细胞。这些发现表明，牛多能干细胞的重编程不完全和/或培养条件不一致/不足。因此，在实现任何预期的iPSC驱动的牛技术之前，有必要进行更多的研究来提高牛多能性的核心知识。牛基因的使用可以成功地重编程小鼠和人类细胞。这些发现表明，牛多能干细胞的重编程不完全和/或培养条件不一致/不足。因此，在实现任何预期的iPSC驱动的牛技术之前，有必要进行更多的研究来提高牛多能性的核心知识。牛基因的使用可以成功地重编程小鼠和人类细胞。这些发现表明，牛多能干细胞的重编程不完全和/或培养条件不一致/不足。因此，在实现任何预期的iPSC驱动的牛技术之前，有必要进行更多的研究来提高牛多能性的核心知识。