一种化学筛选方法可鉴定能在哺乳动物细胞中选择单倍体的化合物。
A Chemical Screen Identifies Compounds Capable of Selecting for Haploidy in Mammalian Cells.
机构信息
Genomic Instability Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain.
Chromosome Dynamics Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain.
出版信息
Cell Rep. 2019 Jul 16;28(3):597-604.e4. doi: 10.1016/j.celrep.2019.06.060.
The recent availability of somatic haploid cell lines has provided a unique tool for genetic studies in mammals. However, the percentage of haploid cells rapidly decreases in these cell lines, which we recently showed is due to their overgrowth by diploid cells present in the cultures. Based on this property, we have now performed a phenotypic chemical screen in human haploid HAP1 cells aiming to identify compounds that facilitate the maintenance of haploid cells. Our top hit was 10-Deacetyl-baccatin-III (DAB), a chemical precursor in the synthesis of Taxol, which selects for haploid cells in HAP1 and mouse haploid embryonic stem cultures. Interestingly, DAB also enriches for diploid cells in mixed cultures of diploid and tetraploid cells, including in the colon cancer cell line DLD-1, revealing a general strategy for selecting cells with lower ploidy in mixed populations of mammalian cells.
最近出现的体单倍体细胞系为哺乳动物的遗传研究提供了独特的工具。然而，这些细胞系中单倍体细胞的比例迅速下降，我们最近的研究表明，这是由于培养物中存在的二倍体细胞过度生长所致。基于这一特性，我们现在在人类单倍体 HAP1 细胞中进行了表型化学筛选，旨在鉴定有助于维持单倍体细胞的化合物。我们的最佳候选物是 10-去乙酰基巴卡丁 III（DAB），这是紫杉醇合成中的一种化学前体，它可选择 HAP1 和小鼠单倍体胚胎干细胞中的单倍体细胞。有趣的是，DAB 还可在包括结肠癌细胞系 DLD-1 在内的二倍体和四倍体细胞的混合培养物中富集二倍体细胞，揭示了一种在哺乳动物细胞混合群体中选择低倍体细胞的通用策略。
Zotero 插件