Evidence map›Paper›PMID 36797484›Full record

ArticleNature microbiology2023

Metabolic heterogeneity and cross-feeding within isogenic yeast populations captured by DILAC.

Stephan Kamrad, Clara Correia-Melo, Lukasz Szyrwiel, Simran Kaur Aulakh, Jürg Bähler, Vadim Demichev, Michael Mülleder, Markus Ralser

Open access · hybridAbstract read
In one paragraph

Article in Nature microbiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
3.8field-weighted citation impact, top 6% of its field
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

17 citing papers in PubMed, 25 citations in OpenAlex.

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  12. Integrative analysis of yeast colony growth.Communications biology · 2024
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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

8 authors at 5 institutions in 2 countries.

Stephan KamradDepartment of Biochemistry, Charité Universitätsmedizin Berlin, Berlin, Germany.ORCID 0000-0002-5957-4661
Clara Correia-MeloDepartment of Biochemistry, Charité Universitätsmedizin Berlin, Berlin, Germany.
Lukasz SzyrwielDepartment of Biochemistry, Charité Universitätsmedizin Berlin, Berlin, Germany.ORCID 0000-0003-1983-2950
Simran Kaur AulakhMolecular Biology of Metabolism Laboratory, The Francis Crick Institute, London, UK.
Jürg BählerInstitute of Healthy Ageing and Department of Genetics, Evolution and Environment, University College London, London, UK.ORCID 0000-0003-4036-1532
Vadim DemichevDepartment of Biochemistry, Charité Universitätsmedizin Berlin, Berlin, Germany.
Michael MüllederCore Facility-High-Throughput Mass Spectrometry, Charité Universitätsmedizin Berlin, Berlin, Germany.
Markus RalserDepartment of Biochemistry, Charité Universitätsmedizin Berlin, Berlin, Germany. markus.ralser@charite.de.ORCID 0000-0001-9535-7413
The Francis Crick Institute · GBBerlin Institute of Health at Charité - Universitätsmedizin Berlin · DECentre for Human Genetics · GBCharité - Universitätsmedizin Berlin · DEUniversity College London · GB

Funding

Cancer Research UK FC001134Medical Research Council FC001134Wellcome Trust FC001134
6 · The paper itself

Abstract

Genetically identical cells are known to differ in many physiological parameters such as growth rate and drug tolerance. Metabolic specialization is believed to be a cause of such phenotypic heterogeneity, but detection of metabolically divergent subpopulations remains technically challenging. We developed a proteomics-based technology, termed differential isotope labelling by amino acids (DILAC), that can detect producer and consumer subpopulations of a particular amino acid within an isogenic cell population by monitoring peptides with multiple occurrences of the amino acid. We reveal that young, morphologically undifferentiated yeast colonies contain subpopulations of lysine producers and consumers that emerge due to nutrient gradients. Deconvoluting their proteomes using DILAC, we find evidence for in situ cross-feeding where rapidly growing cells ferment and provide the more slowly growing, respiring cells with ethanol. Finally, by combining DILAC with fluorescence-activated cell sorting, we show that the metabolic subpopulations diverge phenotypically, as exemplified by a different tolerance to the antifungal drug amphotericin B. Overall, DILAC captures previously unnoticed metabolic heterogeneity and provides experimental evidence for the role of metabolic specialization and cross-feeding interactions as a source of phenotypic heterogeneity in isogenic cell populations.

Indexed as

Amino AcidsSaccharomyces cerevisiaeIsotope LabelingAmino Acids

Identifiers

PMID36797484
PMCPMC9981460
OpenAlexW4321077499

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

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 Socratic graph.