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Copy number variation and selection during reprogramming to pluripotency   总被引:2,自引:0,他引:2  
The mechanisms underlying the low efficiency of reprogramming somatic cells into induced pluripotent stem (iPS) cells are poorly understood. There is a clear need to study whether the reprogramming process itself compromises genomic integrity and, through this, the efficiency of iPS cell establishment. Using a high-resolution single nucleotide polymorphism array, we compared copy number variations (CNVs) of different passages of human iPS cells with their fibroblast cell origins and with human embryonic stem (ES) cells. Here we show that significantly more CNVs are present in early-passage human iPS cells than intermediate passage human iPS cells, fibroblasts or human ES cells. Most CNVs are formed de novo and generate genetic mosaicism in early-passage human iPS cells. Most of these novel CNVs rendered the affected cells at a selective disadvantage. Remarkably, expansion of human iPS cells in culture selects rapidly against mutated cells, driving the lines towards a genetic state resembling human ES cells.  相似文献   
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研究超声波经过两个烧结样品的行为.两个烧结样品为有序的面心立方结构,它们的结构几乎相同.研究表明:在两个有序的准均匀的介质中分别有一个禁带区域.就禁带区域而言,在两个样品中产生禁带的区域非常接近.同时在禁带出现的区域群速度为负值.我们的结果表明群速度的负值的确存在于有序介质中的禁带区域内.  相似文献   
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One of the fascinating aspects of the history of life is the apparent increase in morphological complexity through time, a well known example being mammalian cheek tooth evolution. In contrast, experimental studies of development more readily show a decrease in complexity, again well exemplified by mammalian teeth, in which tooth crown features called cusps are frequently lost in mutant and transgenic mice. Here we report that mouse tooth complexity can be increased substantially by adjusting multiple signalling pathways simultaneously. We cultured teeth in vitro and adjusted ectodysplasin (EDA), activin A and sonic hedgehog (SHH) pathways, all of which are individually required for normal tooth development. We quantified tooth complexity using the number of cusps and a topographic measure of surface complexity. The results show that whereas activation of EDA and activin A signalling, and inhibition of SHH signalling, individually cause subtle to moderate increases in complexity, cusp number is doubled when all three pathways are adjusted in unison. Furthermore, the increase in cusp number does not result from an increase in tooth size, but from an altered primary patterning phase of development. The combination of a lack of complex mutants, the paucity of natural variants with complex phenotypes, and our results of greatly increased dental complexity using multiple pathways, suggests that an increase may be inherently different from a decrease in phenotypic complexity.  相似文献   
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Oldf.  ML 《世界科学》1989,11(8):41-43
世界的生物多样性很大程度上受到传统农业耕作方式的保护。这些生态上复杂的农业系统与作物遗传多样性中心相联系,有传统的栽培品种或“地方品种”,作为世界作物遗传资源的重要组成,还有野生的植物和动物种群,作为生物资源服务于人类。  相似文献   
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