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

Fecha de publicación: Fecha Ahead of Print:

Autores de CIPF

Participantes ajenos a CIPF

  • Tan J
  • Virtue S
  • Norris DM
  • Conway OJ
  • Yang M
  • Bidault G
  • Gribben C
  • Lugtu F
  • Kamzolas I
  • Krycer JR
  • Mills RJ
  • Liang L
  • Pereira C
  • Dale M
  • Shun-Shion AS
  • Baird HJ
  • Horscroft JA
  • Sowton AP
  • Ma M
  • Petsalaki E
  • Murray AJ
  • Gershlick DC
  • Nathan JA
  • Hudson JE
  • Vallier L
  • Fisher-Wellman KH
  • Frezza C
  • Fazakerley DJ

Grupos de Investigación

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 HIF1a 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.

Datos de la publicación

ISSN/ISSNe:
0261-4189, 1460-2075

EMBO JOURNAL  NATURE PUBLISHING GROUP

Tipo:
Article
Páginas:
2127-2165
PubMed:
38580776

Citas Recibidas en Web of Science: 22

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Keywords

  • Cell Culture, Hypoxia, Metabolism/Adipocytes, Oxygen Tension

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