Validation of baboon pluripotent cells as a model for translational stem cell research.

Validation of baboon pluripotent cells as a model for translational stem cell research.
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狒狒多能细胞作为转化干细胞研究模型的验证。

DOI:
10.1016/j.scr.2021.102598
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发表时间:
2021
期刊:
影响因子:
1.2
通讯作者:
McCarrey,JohnR
McCarrey,JohnR
中科院分区:
医学4区
文献类型:
--
作者:
Mahlke,MeganA;Cheng,Keren;Li,Bo;Chaudhari,Shital;Navara,ChristopherS;McCarrey,JohnR

文献摘要

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在适当的临床前模型系统中优化疗效和安全性后,干细胞疗法向临床的转化将是最成功的。在现有的模型中,非人灵长类动物(NHP)提供了最准确的人类解剖学,生理学,遗传学和表观遗传学的重演。在这里,我们表明狒狒多能细胞(PSC)概括了人类PSC的关键分子特征,其准确性高于非灵长类物种(如小鼠)的PSC。具体而言,狒狒和人类PSC表现出更大的基因表达模式的保守性,多能性因子之间更高的序列和结构同源性,更等效的组蛋白和DNA甲基化修饰的全基因组模式,以及与人类和非灵长类PSC之间发现的发育基因的二价编程的类似维持。
Translation of stem cell therapies to the clinic will be most successful following optimization of efficacy and safety in appropriate preclinical model systems. Among available models, nonhuman primates (NHPs) provide the most accurate recapitulation of human anatomy, physiology, genetics and epigenetics. Here, we show that baboon pluripotent cells (PSCs) recapitulate key molecular features of human PSCs with greater accuracy than that found in PSCs from non-primate species such as mice. Specifically, baboon and human PSCs exhibit greater conservation of gene expression patterns, higher sequence and structural homology among pluripotency factors, more equivalent genome-wide patterns of histone and DNA methylation modifications, and similar maintenance of bivalent programming of developmental genes than that found between human and non-primate PSCs.