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A lipid atlas of human and mouse immune cells provides insights into ferroptosis susceptibility.

Pooranee K MorganGerard PernesKevin HuynhCorey GilesSudip PaulAdam Alexander Thil SmithNatalie A MellettAmy LiangTilly van Buuren-MilneCamilla Bertuzzo VeigaThomas J C CollinsYangsong XuMan K S LeeT Michael De SilvaPeter J MeikleGraeme I LancasterAndrew J Murphy
Published in: Nature cell biology (2024)
The cellular lipidome comprises thousands of unique lipid species. Here, using mass spectrometry-based targeted lipidomics, we characterize the lipid landscape of human and mouse immune cells ( www.cellularlipidatlas.com ). Using this resource, we show that immune cells have unique lipidomic signatures and that processes such as activation, maturation and development impact immune cell lipid composition. To demonstrate the potential of this resource to provide insights into immune cell biology, we determine how a cell-specific lipid trait-differences in the abundance of polyunsaturated fatty acid-containing glycerophospholipids (PUFA-PLs)-influences immune cell biology. First, we show that differences in PUFA-PL content underpin the differential susceptibility of immune cells to ferroptosis. Second, we show that low PUFA-PL content promotes resistance to ferroptosis in activated neutrophils. In summary, we show that the lipid landscape is a defining feature of immune cell identity and that cell-specific lipid phenotypes underpin aspects of immune cell physiology.
Keyphrases
  • fatty acid
  • single cell
  • cell death
  • mass spectrometry
  • endothelial cells
  • machine learning
  • genome wide
  • gene expression
  • risk assessment
  • mesenchymal stem cells
  • dna methylation
  • genetic diversity
  • human health