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Lipid mapping of colonic mucosa by cluster TOF-SIMS imaging and multivariate analysis in cftr knockout mice
Authors:Marc Brulet  Alexandre Seyer  Aleksander Edelman  Alain Brunelle  Janine Fritsch  Mario Ollero  Olivier Laprévote
Affiliation:*Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, CNRS, 91198 Gif-sur-Yvette, France;Inserm, U845, Faculté de Médecine Paris Descartes, Paris, France;§Chimie Toxicologie Analytique et Cellulaire, EA 4463, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes, Paris, France
Abstract:
The cftr knockout mouse model of cystic fibrosis (CF) shows intestinal obstruction; malabsorption and inflammation; and a fatty acid imbalance in intestinal mucosa. We performed a lipid mapping of colon sections from CF and control (WT) mice by cluster time of flight secondary-ion mass spectrometry (TOF-SIMS) imaging to localize lipid alterations. Data were processed either manually or by multivariate statistical methods. TOF-SIMS analysis showed a particular localization for cholesteryl sulfate at the epithelial border, C16:1 fatty acid in Lieberkühn glands, and C18:0 fatty acid in lamina propria and submucosa. Significant increases in vitamin E (vE) and C16:0 fatty acid in the epithelial border of CF colon were detected. Principal component analysis (PCA) and partitioning clustering allowed us to characterize different structural regions of colonic mucosa according to variations in C14:0, C16:0, C16:1, C18:0, C18:1, C18:2, C20:3, C20:4, and C22:6 fatty acids; phosphatidylethanolamine, phosphatidylcholine, and phosphatidylinositol glycerolipids; cholesterol; vitamin E; and cholesteryl sulfate. PCA on spectra from Lieberkühn glands led to separation of CF and WT individuals. This study shows for the first time the spatial distribution of lipids in colonic mucosa and suggests TOF-SIMS plus multivariate analyses as a powerful tool to investigate disease-related tissue spatial lipid signatures.
Keywords:time of flight secondary-ion mass spectrometry   mass spectrometry   K-mean   partitioning clustering   principal component analysis
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