Limited oxygen in standard cell culture alters metabolism and function of differentiated cells.
Cell Culture
Hypoxia
Metabolism/Adipocytes
Oxygen Tension
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
05 Apr 2024
05 Apr 2024
Historique:
received:
12
01
2024
accepted:
03
03
2024
revised:
20
02
2024
medline:
6
4
2024
pubmed:
6
4
2024
entrez:
5
4
2024
Statut:
aheadofprint
Résumé
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.
Identifiants
pubmed: 38580776
doi: 10.1038/s44318-024-00084-7
pii: 10.1038/s44318-024-00084-7
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : British Heart Foundation (BHF)
ID : RG/18/7/33636
Organisme : British Heart Foundation (BHF)
ID : FS/17/61/33473
Organisme : British Heart Foundation (BHF)
ID : RG/18/7/33636
Organisme : Wellcome Trust (WT)
ID : PhD Studentship
Organisme : Wellcome Trust (WT)
ID : Sir Henry Dale Fellowship
Organisme : Wellcome Trust (WT)
ID : Senior Clinical Research Fellowship
Organisme : Wellcome Trust (WT)
ID : 204845/Z/16/Z
Organisme : UKRI | Medical Research Council (MRC)
ID : PhD Studentship
Organisme : UKRI | Medical Research Council (MRC)
ID : MRC_MC_UU_12022/6
Organisme : UKRI | Medical Research Council (MRC)
ID : MC_UU_12012/2
Organisme : UKRI | Medical Research Council (MRC)
ID : MR/S007091/1
Organisme : UKRI | Biotechnology and Biological Sciences Research Council (BBSRC)
ID : BB/W005905/1
Organisme : UKRI | Biotechnology and Biological Sciences Research Council (BBSRC)
ID : BB/F016581/1
Organisme : Snow Medical (SnowMedical)
ID : Snow Medical Fellowship
Organisme : EC | ERC | HORIZON EUROPE European Research Council (ERC)
ID : New-Chol
Organisme : DOD | Department of Defense Education Activity (DoDEA)
ID : DOD-W81XWH-19-1-0213
Informations de copyright
© 2024. The Author(s).
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