Episode 58

June 28, 2025

00:22:04

58: Cell competition shapes depletion of aneuploid cells

Hosted by

Gustavo B Barra
58: Cell competition shapes depletion of aneuploid cells
Base by Base
58: Cell competition shapes depletion of aneuploid cells

Jun 28 2025 | 00:22:04

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Show Notes

Fusari E et al., Cell Genomics - Fusari et al. use FLP/FRT–based mosaic methods in Drosophila imaginal epithelia to generate defined segmental monosomies and trisomies and quantify their immediate effects on clonal growth, survival, and interclonal interactions. Key terms: aneuploidy, cell competition, Drosophila, segmental monosomy, trisomy.

Study Highlights:
Using RS- and TSG-FRT tools, the authors show that segmental monosomies of a few hundred genes commonly compromise clonal growth and present signs of outcompetition, whereas trisomies spanning up to ~1,500 genes often lack major autonomous growth defects. Haploinsufficiency of single loci (e.g., RpL26) or cumulative haploinsufficiency of discrete gene sets underlies many monosomy phenotypes. Complementary trisomic clones can exacerbate or rescue monosomy-driven loss, revealing distinct interaction modes including super-competition and lethal competition. The Xrp1–TOR–apoptosis axis and proteotoxic stress partially explain elimination of Rp-containing monosomies.

Conclusion:
Cell-to-cell interactions between complementary aneuploid clones, together with single-gene and cumulative haploinsufficiency, determine the in vivo depletion of aneuploid cells, highlighting cell competition as a key mechanism shaping aneuploid cell fate.

Music:
Enjoy the music based on this article at the end of the episode.

Article title:
Depletion of aneuploid cells is shaped by cell-to-cell interactions

First author:
Fusari E

Journal:
Cell Genomics

DOI:
10.1016/j.xgen.2025.100894

Reference:
Fusari E, Muzzopappa M, Gracia J, Milán M. Depletion of aneuploid cells is shaped by cell-to-cell interactions. Cell Genomics. 2025;5:100894. https://doi.org/10.1016/j.xgen.2025.100894

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

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Episode link: https://basebybase.com/episodes/papercast-base-by-base-58

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2025-06-28.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited the transcript sections describing the in vivo mosaic aneuploidy model in Drosophila imaginal discs, the Twin Spot Generator (TSG) and RS-FRT approaches, cell competition modalities (lethal, super-competition, compensatory proliferation), region-specific monosomy/trisomy findings (regions 1 and 2), and implicat
- transcript topics: In vivo mosaic aneuploidy in Drosophila imaginal discs; Twin Spot Generator (TSG) and RS-FRT recombination; Segmental monosomies and trisomies effects on growth; Cell competition: lethal competition, super-competition, compensatory proliferation; Region 1 (72A1–73A5) and flower gene–mediated competition; Region 2: compensatory proliferation and martyr signaling

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 6
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- Monosomies are outcompeted by neighboring euploid cells, leading to their elimination via cell competition.
- Trisomies up to around 1,500 genes generally do not show major autonomous growth defects in vivo.
- Complementary monosomies and trisomies can exacerbate or rescue monosomy-driven loss, showing region-specific interactions (e.g., region 1 super-competition; region 2 compensatory
- Region 1 contains a ~179-gene interval (72A1–73A5) with the flower gene implicated in competition, contributing to super-competition in trisomies.
- Region 2 exhibits compensatory proliferation where trisomic cells die and secrete signals that rescue monosomic neighbors.
- The XRP1–TOR–apoptosis axis and proteotoxic stress contribute to monosomy elimination; Xrp1 and mTor manipulations can modulate outcomes.

QC result: Pass.

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