PXD036959

PXD036959 is an original dataset announced via ProteomeXchange.

Title	Differential isotope labelling by amino acids (DILAC) reveals metabolic cross-feeding and phenotypic heterogeneity in a clonal cell population
Description	Genetically identical cells are known to differ in many physiological parameters such as growth rate and drug tolerance, but the source of such heterogeneity is often insufficiently understood. Exchange interactions between metabolite producing and consuming cells are believed to be one possible cause, but detecting metabolically divergent subpopulations remains technically challenging. We developed a proteomics-based technology, termed differential isotope labelling by amino acids (DILAC), which monitors amino acid incorporation into peptides with multiple occurrences of the same amino acid. DILAC is used to differentiate producer and consumer cells of a particular amino acid within an isogenic cell population. We applied DILAC to young, morphologically undifferentiated yeast colonies and reveal that they contain sub-populations of lysine producers and consumers which emerge due to nutrient gradients. DILAC can deconvolute the proteome of subpopulations from bulk measurements which indicated an in situ cross feeding situation where fast growing cells ferment and provide the slower growing, respiring cells with ethanol as substrate. Finally, by combining DILAC with FACS, we show that the metabolic states that differ between isogenic cells, confer resistance to the antifungal drug amphotericin B. Overall, this novel and broadly applicable methodological approach captures previously unnoticed metabolic heterogeneity, providing experimental evidence for the role of metabolic specialisation and cross-feeding interactions as a source of phenotypic heterogeneity in isogenic cell populations.
HostingRepository	PanoramaPublic
AnnounceDate	2023-02-17
AnnouncementXML	Submission_2023-02-17_09:41:53.109.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	supported by repository but incomplete data and/or metadata
PrimarySubmitter	Stephan Kamrad
SpeciesList	scientific name: Saccharomyces cerevisiae; NCBI TaxID: 4932;
ModificationList	SPITC:13C(6); Label:13C(6); Label:13C(9)
Instrument	TripleTOF 6600

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-24 15:26:01	ID requested
⏵ 1	2023-02-17 09:41:53	announced

Stephan Kamrad, Clara Correia-Melo, Lukasz Szyrwiel, Simran Kaur Aulakh, Jürg Bähler, Vadim Demichev, Michael Mülleder and Markus Ralser (2023). "Metabolic heterogeneity and cross-feeding within isogenic yeast populations captured by DILAC". Nature Microbiology

submitter keyword: 13C, yeast, heterogeneity, subpopulations, PRM, DILAC

Markus Ralser
contact affiliation	Charité – Universitätsmedizin Berlin
contact email	markus.ralser@charite.de
lab head
Stephan Kamrad
contact affiliation	The Francis Crick Institute
contact email	stephan.kamrad@gmail.com
dataset submitter

Panorama Public dataset URI