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

Authors :
Joycelyn Tan
Sam Virtue
Dougall M. Norris
Olivia J. Conway
Ming Yang
Christopher Gribben
Fatima Lugtu
Ioannis Kamzolas
James R. Krycer
Richard J. Mills
Conceição Pereira
Martin Dale
Amber S. Shun-Shion
Harry J. M. Baird
James A. Horscroft
Alice P. Sowton
Marcella Ma
Stefania Carobbio
Evangelia Petsalaki
Andrew J. Murray
David C. Gershlick
James E. Hudson
Ludovic Vallier
Kelsey H Fisher-Wellman
Christian Frezza
Antonio Vidal-Puig
Daniel J. Fazakerley
Publication Year :
2022
Publisher :
Cold Spring Harbor Laboratory, 2022.

Abstract

SUMMARYCell 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.

Details

Database :
OpenAIRE
Accession number :
edsair.doi...........0fe7ad781bc0666a5a17fe82ad499dc9