Cell reprogramming and early embryo development

破译胚胎如何开始调节它们的发育，以及细胞如何开始分化形成新的有机体，是生物学研究的一个基本领域，以更好地了解不同物种如何繁殖和繁殖。最近，胚胎发育、细胞分化和重新编程已成为开发新的细胞疗法和辅助生殖技术应用于动物和人类的领先研究课题。例如，基于胚胎的技术已被应用于缓解人类和动物的生育问题，加快动物育种和家畜选择计划，以及帮助繁殖和保护濒危物种。同样，诱导细胞重新编程和分化的能力使细胞的生产在受损细胞和组织的再生方面具有很好的应用前景。然而，尽管最近在这些领域取得了显著的研究进展，但仍有许多工作要做。例如，为什么有相当大比例的胚胎在很少的细胞分裂后停止发育，目前还不清楚。此外，通过核移植诱导完全细胞重编程的效率仍然很低，这是最初用于证明哺乳动物细胞分化过程是可逆的方法。此外，协调早期发育和细胞重编程的基本机制在不同物种中是否相同，目前仍在很大程度上尚不清楚。为了帮助找到这些重要生物学问题的答案，我的研究计划将研究猪早期胚胎发育和细胞重新编程的调控，因为它与食物生产相关，也是研究人类生理和疾病以及开发和测试新疗法的代表性动物模型。我们的具体目标是确定早期发育的胚胎如何通过激活其基因组中编码的基因来获得控制其发育的能力，以及它们如何启动细胞分化。此外，我们计划通过在培养的体细胞和核移植胚胎中表达胚胎因子来增加细胞重编程。这项研究将为猪早期胚胎发育的调控提供新的知识。此外，这项研究还可能导致胚胎因素的确定，这些因素是产仔数和繁殖力的有用选择标记，是猪生产中最需要的性状。这将对加拿大养猪业产生巨大影响，加拿大是全球第五大猪肉出口国，2017年猪肉出口量约为13亿吨，价值40亿美元。随着对细胞重编程的更好理解，SCNT技术的效率也可能提高多能和全能细胞的产量，这对开发用于生物医学的新的猪谱系以及物种保护具有重要意义。

Deciphering how embryos start regulating their development and cells begin differentiating to form a new organism is a fundamental field of research in biology to better understand how the different species reproduce and propagate. More recently, embryo development, cell differentiation and reprogramming have emerged as leading research topics for development of new cell therapies and assisted reproductive technologies for applications in animals and humans. For instance, embryo-based technologies have been applied to mitigate fertility issues in humans and animals, to accelerate animal breeding and selection programs in livestock, and to help reproducing and preserving endangered species. Similarly, the capacity to induce cell reprogramming and differentiation has enabled the production of cells having promising applications for regeneration of damaged cell and tissues. However, despite of remarkable recent research advances in these fields, much remains to be done. For example, it is still unknown why a significant proportion of embryos arrest developing after few cell divisions. In addition, the efficiency to induce complete cell reprogramming by nuclear transfer, the original method used to demonstrate that the cell differentiation process is reversible in mammals, is still very low. Moreover, it is still largely unknown if the fundamental mechanisms coordinating early development and cell reprogramming are the same in different species. To help finding answers to these important biology questions, my research program will study the regulation of early embryo development and cell reprogramming in pigs given its relevance for food production and also as a representative animal model for studying human physiology and disease, and for the development and testing of new therapies. Our specific goals are to determine how early developing embryos acquire the capacity to control their development by activating genes encoded in their genome and how they initiate cell differentiation. In addition, we plan to increase cell reprogramming by expressing embryonic factors in cultured somatic cells and in nuclear transfer embryos. The proposed research will contribute new knowledge on the regulation of early embryo development in pigs. In addition, this research may lead to the identification of embryo factors, which are useful selection markers for litter size and prolificity, the top traits desired in swine production. This would have a tremendous impact on the Canadian swine industry, the 5th largest pork exporter with ~1.3 billion tons and >$4 billion dollars, in 2017. With better understanding of cell reprogramming, the efficiency of SCNT technology may also improve production of pluripotent and totipotent cells and this has important implications for the development of new swine lineages for biomedical applications as well as for species conservation.