A Chemical Screen Identifies Compounds Capable of Selecting for Haploidy in Mammalian Cells

Summary: 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. : Cultures of haploid animal cell lines become progressively enriched in diploid cells. By conducting a chemical screen in HAP1 cells, Olbrich et al. identify compounds that facilitate the maintenance of haploid cells and a general strategy to select for cells with lower ploidy in mixed cultures of mammalian cells. Keywords: chemical screen, haploidy, tetraploidy, 10-Deacetylbaccatin-III, paclitaxel, mitosis