Evidence map›Paper›PMID 38580776›Full record

ArticleThe EMBO journal2024

Limited oxygen in standard cell culture alters metabolism and function of differentiated cells.

Joycelyn Tan, Sam Virtue, Dougall M Norris, Olivia J Conway, Ming Yang, Guillaume Bidault, Christopher Gribben, Fatima Lugtu, Ioannis Kamzolas, James R Krycer and 20 more

Erratum issuedOpen access · diamondAbstract read
In one paragraph

Article in The EMBO journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
13.1field-weighted citation impact, top 1% 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

40 citing papers in PubMed, 47 citations in OpenAlex.

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  20. WhenAPL bioengineering · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors at 5 institutions in 5 countries.

Joycelyn Tan *Metabolic Research Laboratories, Wellcome-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, CB2 0QQ, UK.ORCID http://orcid.org/0000-0001-8531-5455
Sam Virtue *Metabolic Research Laboratories, Wellcome-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, CB2 0QQ, UK. sv234@cantab.ac.uk.ORCID http://orcid.org/0000-0002-9545-5432
Dougall M Norris *Metabolic Research Laboratories, Wellcome-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, CB2 0QQ, UK.
Olivia J ConwayMetabolic Research Laboratories, Wellcome-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, CB2 0QQ, UK.
Ming YangMRC Cancer Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0XZ, UK.
Guillaume BidaultMetabolic Research Laboratories, Wellcome-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, CB2 0QQ, UK.
Christopher GribbenWellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, CB2 0AW, UK.
Fatima LugtuWellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, CB2 0AW, UK.ORCID http://orcid.org/0000-0003-2084-609X
Ioannis KamzolasMetabolic Research Laboratories, Wellcome-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, CB2 0QQ, UK.ORCID http://orcid.org/0000-0002-7408-5284
James R KrycerQIMR Berghofer Medical Research Institute, Brisbane, Queensland, 4006, Australia.ORCID http://orcid.org/0000-0003-1536-7270
Richard J MillsQIMR Berghofer Medical Research Institute, Brisbane, Queensland, 4006, Australia.
Lu LiangMetabolic Research Laboratories, Wellcome-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, CB2 0QQ, UK.
Conceição PereiraCambridge Institute for Medical Research, University of Cambridge, Cambridge, CB2 0XY, UK.ORCID http://orcid.org/0000-0003-0164-4169
Martin DaleMetabolic Research Laboratories, Wellcome-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, CB2 0QQ, UK.
Amber S Shun-ShionMetabolic Research Laboratories, Wellcome-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, CB2 0QQ, UK.
Harry Jm BairdMetabolic Research Laboratories, Wellcome-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, CB2 0QQ, UK.ORCID http://orcid.org/0000-0003-0763-3786
James A HorscroftDepartment of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3EL, UK.
Alice P SowtonDepartment of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3EL, UK.ORCID http://orcid.org/0000-0002-3718-7783
Marcella MaMetabolic Research Laboratories, Wellcome-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, CB2 0QQ, UK.ORCID http://orcid.org/0000-0002-2228-7466
Stefania CarobbioMetabolic Research Laboratories, Wellcome-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, CB2 0QQ, UK.ORCID http://orcid.org/0000-0001-6631-7930
Evangelia PetsalakiEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, CB10 1SD, UK.ORCID http://orcid.org/0000-0002-8294-2995
Andrew J MurrayDepartment of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3EL, UK.ORCID http://orcid.org/0000-0002-0929-9315
David C GershlickCambridge Institute for Medical Research, University of Cambridge, Cambridge, CB2 0XY, UK.ORCID http://orcid.org/0000-0002-0602-210X
James A NathanCambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, Department of Medicine, University of Cambridge, Cambridge, CB2 0AW, UK.ORCID http://orcid.org/0000-0002-0248-1632
James E HudsonQIMR Berghofer Medical Research Institute, Brisbane, Queensland, 4006, Australia.
Ludovic VallierWellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, CB2 0AW, UK.ORCID http://orcid.org/0000-0002-3848-2602
Kelsey H Fisher-WellmanDepartment of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, 27834, USA.ORCID http://orcid.org/0000-0002-0300-829X
Christian FrezzaMRC Cancer Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0XZ, UK.ORCID http://orcid.org/0000-0002-3293-7397
Antonio Vidal-PuigMetabolic Research Laboratories, Wellcome-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, CB2 0QQ, UK. ajv22@medschl.cam.ac.uk.ORCID http://orcid.org/0000-0003-4220-9577
Daniel J FazakerleyMetabolic Research Laboratories, Wellcome-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, CB2 0QQ, UK. djf72@medschl.cam.ac.uk.ORCID http://orcid.org/0000-0001-8241-2903
University of Cambridge · GBQueensland University of Technology · AUWellcome/MRC Cambridge Stem Cell Institute · GBEuropean Bioinformatics Institute · GBUniversity of North Carolina at Chapel Hill · US

Funding

British Heart Foundation (BHF) FS/17/61/33473British Heart Foundation (BHF) RG/18/7/33636DOD | Department of Defense Education Activity (DoDEA) DOD-W81XWH-19-1-0213EC | ERC | HORIZON EUROPE European Research Council (ERC) New-CholMedical Research Council MC_UU_00014/5Snow Medical (SnowMedical) Snow Medical FellowshipUKRI | Biotechnology and Biological Sciences Research Council (BBSRC) BB/F016581/1UKRI | Biotechnology and Biological Sciences Research Council (BBSRC) BB/W005905/1UKRI | Medical Research Council (MRC) MC_UU_12012/2UKRI | Medical Research Council (MRC) MRC_MC_UU_12022/6UKRI | Medical Research Council (MRC) MR/S007091/1UKRI | Medical Research Council (MRC) PhD StudentshipWellcome TrustWellcome Trust (WT) 204845/Z/16/ZWellcome Trust (WT) PhD StudentshipWellcome Trust (WT) Senior Clinical Research FellowshipWellcome Trust (WT) Sir Henry Dale Fellowship
6 · The paper itself

Abstract

The in vitro oxygen microenvironment profoundly affects the capacity of cell cultures to model physiological and pathophysiological states. Cell culture is often considered to be hyperoxic, but pericellular oxygen levels, which are affected by oxygen diffusivity and consumption, are rarely reported. Here, we provide evidence that several cell types in culture actually experience local hypoxia, with important implications for cell metabolism and function. We focused initially on adipocytes, as adipose tissue hypoxia is frequently observed in obesity and precedes diminished adipocyte function. Under standard conditions, cultured adipocytes are highly glycolytic and exhibit a transcriptional profile indicative of physiological hypoxia. Increasing pericellular oxygen diverted glucose flux toward mitochondria, lowered HIF1α activity, and resulted in widespread transcriptional rewiring. Functionally, adipocytes increased adipokine secretion and sensitivity to insulin and lipolytic stimuli, recapitulating a healthier adipocyte model. The functional benefits of increasing pericellular oxygen were also observed in macrophages, hPSC-derived hepatocytes and cardiac organoids. Our findings demonstrate that oxygen is limiting in many terminally-differentiated cell types, and that considering pericellular oxygen improves the quality, reproducibility and translatability of culture models.

Indexed as

AdipocytesCell DifferentiationOxygenAnimalsCell Culture TechniquesCell HypoxiaCells, CulturedGlucoseGlycolysisHepatocytesHumansHypoxia-Inducible Factor 1, alpha SubunitMacrophagesMiceMitochondriaGlucoseHypoxia-Inducible Factor 1, alpha SubunitOxygenCell CultureHypoxiaMetabolism/AdipocytesOxygen Tension

Identifiers

PMID38580776
PMCPMC11148168
OpenAlexW4393991564

What OpenQuestion holds

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Registered trials

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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.