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

Teresa Olbrich; Maria Vega-Sendino; Matilde Murga; Guillermo de Carcer; Marcos Malumbres; Sagrario Ortega; Sergio Ruiz; Oscar Fernandez-Capetillo

doi:10.1016/j.celrep.2019.06.060

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

Cell Rep. 2019 Jul 16;28(3):597-604.e4. doi: 10.1016/j.celrep.2019.06.060.

Authors

Teresa Olbrich¹, Maria Vega-Sendino¹, Matilde Murga¹, Guillermo de Carcer², Marcos Malumbres², Sagrario Ortega³, Sergio Ruiz¹, Oscar Fernandez-Capetillo⁴

Affiliations

¹ Genomic Instability Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain.
² Chromosome Dynamics Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain.
³ Transgenics Unit, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain.
⁴ Genomic Instability Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain; Science for Life Laboratory, Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, 171 21 Stockholm, Sweden. Electronic address: ofernandez@cnio.es.

Abstract

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.

Keywords: 10-Deacetylbaccatin-III; chemical screen; haploidy; mitosis; paclitaxel; tetraploidy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line
Cell Line, Tumor
Cell Separation
Diploidy
Embryonic Stem Cells / cytology*
Embryonic Stem Cells / metabolism
Haploidy*
High-Throughput Screening Assays / methods*
Humans
Mice
Mitosis / drug effects
Mitosis / genetics
Ploidies*
Taxoids / chemistry
Taxoids / pharmacology*

Substances

Taxoids
10-deacetylbaccatine III