Cell competition removes segmental aneuploid cells from Drosophila imaginal disc-derived tissues based on ribosomal protein gene dose

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...

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Main Authors: Zhejun Ji, Jacky Chuen, Marianthi Kiparaki, Nicholas Baker
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2021-04-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/61172
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spelling doaj-81c5fc7ac16c4f4989dc49c946e427f12021-05-05T22:58:39ZengeLife Sciences Publications LtdeLife2050-084X2021-04-011010.7554/eLife.61172Cell competition removes segmental aneuploid cells from Drosophila imaginal disc-derived tissues based on ribosomal protein gene doseZhejun Ji0Jacky Chuen1https://orcid.org/0000-0003-4781-6907Marianthi Kiparaki2Nicholas Baker3https://orcid.org/0000-0002-4250-3488Department of Genetics, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Genetics, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Genetics, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Genetics, Albert Einstein College of Medicine, Bronx, United StatesAneuploidy 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 eIF2γ 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.https://elifesciences.org/articles/61172aneuploidycell competitionMinuteribosomal protein mutation
collection DOAJ
language English
format Article
sources DOAJ
author Zhejun Ji
Jacky Chuen
Marianthi Kiparaki
Nicholas Baker
spellingShingle Zhejun Ji
Jacky Chuen
Marianthi Kiparaki
Nicholas Baker
Cell competition removes segmental aneuploid cells from Drosophila imaginal disc-derived tissues based on ribosomal protein gene dose
eLife
aneuploidy
cell competition
Minute
ribosomal protein mutation
author_facet Zhejun Ji
Jacky Chuen
Marianthi Kiparaki
Nicholas Baker
author_sort Zhejun Ji
title Cell competition removes segmental aneuploid cells from Drosophila imaginal disc-derived tissues based on ribosomal protein gene dose
title_short Cell competition removes segmental aneuploid cells from Drosophila imaginal disc-derived tissues based on ribosomal protein gene dose
title_full Cell competition removes segmental aneuploid cells from Drosophila imaginal disc-derived tissues based on ribosomal protein gene dose
title_fullStr Cell competition removes segmental aneuploid cells from Drosophila imaginal disc-derived tissues based on ribosomal protein gene dose
title_full_unstemmed Cell competition removes segmental aneuploid cells from Drosophila imaginal disc-derived tissues based on ribosomal protein gene dose
title_sort cell competition removes segmental aneuploid cells from drosophila imaginal disc-derived tissues based on ribosomal protein gene dose
publisher eLife Sciences Publications Ltd
series eLife
issn 2050-084X
publishDate 2021-04-01
description 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 eIF2γ 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.
topic aneuploidy
cell competition
Minute
ribosomal protein mutation
url https://elifesciences.org/articles/61172
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