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Limited oxygen availability in standard cell culture alters metabolism and function in terminally differentiated cells

ABSTRACT:

Cell culture is generally considered to be hyperoxic. However, the importance of cellular oxygen consumption is often underappreciated, with rates of oxygen consumption often sufficient to cause hypoxia at cell monolayers. We initially focused on cultured adipocytes as a terminally differentiated cell-type with substantial oxygen consumption rates to support diverse cellular functions. Under standard conditions, cultured adipocytes are hypoxic and highly glycolytic. Increasing oxygen diverted glucose flux toward mitochondria and resulted in thousands of gene expression changes that pointed toward alleviated physiological transcriptional responses to hypoxia. Phenotypically, providing more oxygen increased adipokine secretion and rendered adipocytes more sensitive to insulin and lipolytic stimuli. The functional benefits of increasing pericellular oxygen were transferable to other cellular systems including hPSC-derived hepatocytes and cardiac organoids. Our findings suggest that oxygen is limiting in many terminally-differentiated cell culture systems, and that controlling oxygen availability can improve the quality and translatability of cell models.

INSTRUMENT(S): Liquid Chromatography MS - alternating - hilic

SUBMITTER: Joycelyn Tan

PROVIDER: MTBLS6677 | MetaboLights | 2024-02-21

REPOSITORIES: MetaboLights

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			Action	DRS
	MTBLS6677	Other
	FILES	Other
	a_MTBLS6677_LC-MS_alternating_hilic_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS6677_LC-MS_alternating_hilic_metabolite_profiling_v2_maf.tsv	Tabular

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