Evidence map›Paper›PMID 40632871›Full record

ArticleScience advances2025

Sensing of extracellular l-proline availability by the integrated stress response determines the outcome of cell competition.

Shruthi Krishnan, Ana Lima, Sizhe Tan, Ying Thong Low, Salvador Perez Montero, Aida Di Gregorio, Adrian Perez Barreto, Sarah Bowling, Karen Vousden, Tristan A Rodriguez

Abstract read
In one paragraph

Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Shruthi KrishnanNational Heart and Lung Institute, Imperial College London, London, UK.ORCID 0009-0006-0128-801X
Ana LimaNational Heart and Lung Institute, Imperial College London, London, UK.ORCID 0000-0002-2821-7178
Sizhe TanNational Heart and Lung Institute, Imperial College London, London, UK.ORCID 0009-0003-1292-8113
Ying Thong LowThe Francis Crick Institute, London, UK.ORCID 0009-0001-7804-7787
Salvador Perez MonteroNational Heart and Lung Institute, Imperial College London, London, UK.ORCID 0000-0002-1277-2660
Aida Di GregorioNational Heart and Lung Institute, Imperial College London, London, UK.
Adrian Perez BarretoNational Heart and Lung Institute, Imperial College London, London, UK.ORCID 0009-0005-9795-6192
Sarah BowlingDepartment of Developmental Biology, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0002-4997-3052
Karen VousdenThe Francis Crick Institute, London, UK.ORCID 0000-0002-7365-1766
Tristan A RodriguezNational Heart and Lung Institute, Imperial College London, London, UK.ORCID 0000-0002-3415-8493

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cell competition is a conserved fitness quality control that eliminates cells that are less fit than their neighbors. How winner cells induce the elimination of losers is poorly understood. We tackle this question by studying the onset of embryonic differentiation in mice, where cell competition eliminates 35% of embryonic cells. These loser cells have mitochondrial dysfunction, which we show causes amino acid deprivation and activation of the integrated stress response (ISR), a pathway essential for their survival. We demonstrate that l-proline is a key amino acid sensed by the ISR and that proline represses the ISR and drives their elimination. These results indicate that cell competition acts as a previously unidentified tissue-sparing mechanism, regulated by the availability of extracellular amino acids, that allows for the elimination of dysfunctional cells when amino acids are plentiful but ensures their survival in nutrient-poor environments.

Indexed as

ProlineStress, PhysiologicalAnimalsCell DifferentiationMiceMitochondriaProline

Identifiers

PMID40632871
PMCPMC12239963

What OpenQuestion holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.