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Systems biology discoveries using non-human primate pluripotent stem and germ cells: novel gene and genomic imprinting interactions as well as unique expression patterns

机译:使用非人类灵长类动物多能干细胞和生殖细胞的系统生物学发现:新的基因和基因组印迹相互作用以及独特的表达方式

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摘要

The study of pluripotent stem cells has generated much interest in both biology and medicine. Understanding the fundamentals of biological decisions, including what permits a cell to maintain pluripotency, that is, its ability to self-renew and thereby remain immortal, or to differentiate into multiple types of cells, is of profound importance. For clinical applications, pluripotent cells, including both embryonic stem cells and adult stem cells, have been proposed for cell replacement therapy for a number of human diseases and disorders, including Alzheimer's, Parkinson's, spinal cord injury and diabetes. One challenge in their usage for such therapies is understanding the mechanisms that allow the maintenance of pluripotency and controlling the specific differentiation into required functional target cells. Because of regulatory restrictions and biological feasibilities, there are many crucial investigations that are just impossible to perform using pluripotent stem cells (PSCs) from humans (for example, direct comparisons among panels of inbred embryonic stem cells from prime embryos obtained from pedigreed and fertile donors; genomic analysis of parent versus progeny PSCs and their identical differentiated tissues; intraspecific chimera analyses for pluripotency testing; and so on). However, PSCs from nonhuman primates are being investigated to bridge these knowledge gaps between discoveries in mice and vital information necessary for appropriate clinical evaluations. In this review, we consider the mRNAs and novel genes with unique expression and imprinting patterns that were discovered using systems biology approaches with primate pluripotent stem and germ cells.
机译:多能干细胞的研究引起了生物学和医学上的极大兴趣。理解生物学决定的基础,包括使细胞保持多能性的条件,即其自我更新并因此保持永生或分化为多种类型细胞的能力,具有极为重要的意义。对于临床应用,已经提出了包括胚胎干细胞和成体干细胞在内的全能细胞用于多种人类疾病和病症的细胞替代疗法,包括阿尔茨海默氏症,帕金森氏症,脊髓损伤和糖尿病。在其用于此类疗法中的一个挑战是理解允许维持多能性并控制向所需功能靶细胞的特异性分化的机制。由于监管限制和生物学可行性,使用人类多能干细胞(PSC)不可能进行许多重要的研究(例如,直接杂交从纯种和可育供体获得的原始胚胎中分离的近交胚胎干细胞) ;亲本和子代PSC及其相同的分化组织的基因组分析;用于多能性测试的种内嵌合体分析;等等。但是,正在研究非人类灵长类动物的PSC,以弥合小鼠发现与适当临床评估所需的重要信息之间的这些知识鸿沟。在这篇综述中,我们考虑了具有灵长类多能干细胞和生殖细胞的系统生物学方法发现的具有独特表达和印迹模式的mRNA和新基因。

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