@article{abb52f51adfa467d9450d54f4b84f264,
title = "Cell competition removes segmental aneuploid cells from drosophila imaginal disc-derived tissues based on ribosomal protein gene dose",
abstract = "Aneuploidy causes birth defects and miscarriages, occurs in nearly all cancers and is a hallmark of aging. Individual aneuploid cells can be eliminated from developing tissues by unknown mechanisms. Cells with ribosomal protein (Rp) gene mutations are also eliminated, by cell competition with normal cells. Because Rp genes are spread across the genome, their copy number is a potential marker for aneuploidy. We found that elimination of imaginal disc cells with irradiation-induced genome damage often required cell competition genes. Segmentally aneuploid cells derived from targeted chromosome excisions were eliminated by the RpS12-Xrp1 cell competition pathway if they differed from neighboring cells in Rp gene dose, whereas cells with normal doses of the Rp and eIF2g genes survived and differentiated adult tissues. Thus, cell competition, triggered by differences in Rp gene dose between cells, is a significant mechanism for the elimination of aneuploid somatic cells, likely to contribute to preventing cancer.",
author = "Zhejun Ji and Jacky Chuen and Marianthi Kiparaki and Nicholas Baker",
note = "Funding Information: We thank Jorge Blanco, Michael Brodsky, Kevin Cook, Kent Golic, and Cristina Montagna for useful discussions, Tao Wang for statistical advice, and D Rio for Xrp1-specific antibodies. This study would not have been possible without genetic strains obtained from the Exelixis Collection at Harvard Medical School and from the Bloomington Drosophila Stock Center (supported by NIH P40OD018537). We also thank Erika Bach, Susan Celniker, and Gunter Reuter for genetic strains. We thank S Emmons, J Hebert, A Jenny, M Kiparaki, A Kumar, C Montagna, J Secombe, and A Tomlin-son for comments on this or earlier versions of the manuscript. Supported by a grant from the NIH (GM104213). Confocal Imaging was performed at the Analytical Imaging Facility, Albert Einstein College of Medicine, supported by NCI cancer center support grant (P30CA013330), using Leica SP5 and SP8 microscopes, the latter acquired through NIH SIG 1S10 OD023591. This paper includes data from a thesis partially fulfilling of the requirements for the Degree of Doctor of Philosophy in the Graduate Division of Medical Sciences, Albert Einstein College of Medicine, Yeshiva University. Funding Information: We thank Jorge Blanco, Michael Brodsky, Kevin Cook, Kent Golic, and Cristina Montagna for useful discussions, Tao Wang for statistical advice, and D Rio for Xrp1-specific antibodies. This study would not have been possible without genetic strains obtained from the Exelixis Collection at Harvard Medical School and from the Bloomington Drosophila Stock Center (supported by NIH P40OD018537). We also thank Erika Bach, Susan Celniker, and Gunter Reuter for genetic strains. We thank S Emmons, J Hebert, A Jenny, M Kiparaki, A Kumar, C Montagna, J Secombe, and A Tomlinson for comments on this or earlier versions of the manuscript. Supported by a grant from the NIH (GM104213). Confocal Imaging was performed at the Analytical Imaging Facility, Albert Einstein College of Medicine, supported by NCI cancer center support grant (P30CA013330), using Leica SP5 and SP8 microscopes, the latter acquired through NIH SIG 1S10 OD023591. This paper includes data from a thesis partially fulfilling of the requirements for the Degree of Doctor of Philosophy in the Graduate Division of Medical Sciences, Albert Einstein College of Medicine, Yeshiva University. Publisher Copyright: {\textcopyright} Ji et al.",
year = "2021",
doi = "10.7554/ELIFE.61172",
language = "English (US)",
volume = "10",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}
