Sphingolipid | EPFL Graph Search

Sphingolipids are a class of lipids containing a backbone of sphingoid bases, which are a set of aliphatic amino alcohols that includes sphingosine. They were discovered in brain extracts in the 1870s and were named after the mythological sphinx because of their enigmatic nature. These compounds play important roles in signal transduction and cell recognition. Sphingolipidoses, or disorders of sphingolipid metabolism, have particular impact on neural tissue. A sphingolipid with a terminal hydroxyl group is a ceramide. Other common groups bonded to the terminal oxygen atom include phosphocholine, yielding a sphingomyelin, and various sugar monomers or dimers, yielding cerebrosides and globosides, respectively. Cerebrosides and globosides are collectively known as glycosphingolipids. Structure The long-chain bases, sometimes simply known as sphingoid bases, are the first non-transient products of de novo sphingolipid synthesis in both yeast and mammals. These compounds, spec

Single-cell lipidomics reveals a role for cell-to-cell sphingolipid heterogeneity in fibroblast activation

Laura Capolupo

Cell-to-cell variability plays a key role in tissue patterning by setting initial asymmetry that primes cell fate decisions. Fluctuations in the activity of regulatory molecules can commit individual cells to divergent differentiation pathways, and cell-to-cell variability can diversify the response of an otherwise homogeneous cell community to its environment. Recent advances have provided scientists with tools to study the variability associated with individual cells. However, while single-cell data are available for genomes, transcriptomes and proteomes, they are scarce for metabolic products, such as lipids. Eukaryotic cells produce thousands of lipids â each potentially contributing to specific biological functions. Furthermore, a number of metabolic switches involving lipids have been described to occur in development and cell differentiation. Few studies have directly addressed cell-to-cell lipid variations in syngeneic cell populations suggesting that lipid heterogeneity contributes to the emergence of multicellular patterns. Nonetheless, lipid biologists have so far addressed lipidomes in bulk cell extracts or selected lipids at the single-cell level. Thus, how lipidomes vary from one cell to another and which cell-to-cell lipid variations have biological meaning remains to be defined. Recent developments have provided mass spectrometry with sufficient sensitivity to reveal molecules in few hundred copies, making single-cell lipidomics possible. A rapidly emerging technique with a potential use in single-cell lipidomics is imaging mass spectrometry. Here, we devised a high-resolution MALDI imaging mass spectrometry pipeline to study cell-to-cell variability of the lipidome of hundreds of primary dermal human fibroblasts. We found that sphingolipid metabolism shows high cell-to-cell heterogeneity and that specific sphingolipids mark distinct cell sub-populations: coined herein as âlipotypesâ. Furthermore, we found that fibroblast lipotypes correspond to cell states endowed with proliferative, inflammatory or fibrogenic properties. Finally, we asked whether lipotypes participate in the specification of cell states and find that specific glycosphingolipids modulate signalling pathways (i.e., the FGF and TGF-b) to shape the transcriptional cell landscape. In summary, through the use of single-cell omics techniques, we found that: (i) specific lipid metabolic segments (i.e., the sphingolipid pathways) have cell-to-cell variation; (ii) given lipid configurations mark discrete cell states; and (iii) sphingolipids modulate dermal fibroblast activation involved in wound healing and skin homeostasis. Altogether, this study is among the first to demonstrate the potential of MALDI-IMS for single-cell lipidomics and to reveal cell-to-cell lipidome heterogeneity. It also demonstrates a role for lipids in the determination of cell states and in tissue patterning and reveals a new regulatory component to the self-organization of multicellular systems.

EPFL2021

Flagellar membranes are rich in raft-forming phospholipids

Adrian Schmid

The observation that the membranes of flagella are enriched in sterols and sphingolipids has led to the hypothesis that flagella might be enriched in raft-forming lipids. However, a detailed lipidomic analysis of flagellar membranes is not available. Novel protocols to detach and isolate intact flagella from Trypanosoma brucei procyclic forms in combination with reverse-phase liquid chromatography high-resolution tandem mass spectrometry allowed us to determine the phospholipid composition of flagellar membranes relative to whole cells. Our analyses revealed that phosphatidylethanolamine, phosphatidylserine, ceramide and the sphingolipids inositol phosphorylceramide and sphingomyelin are enriched in flagella relative to whole cells. In contrast, phosphatidylcholine and phosphatidylinositol are strongly depleted in flagella. Within individual glycerophospholipid classes, we observed a preference for ether-type over diacyl-type molecular species in membranes of flagella. Our study provides direct evidence for a preferential presence of raft-forming phospholipids in flagellar membranes of T. brucei.

Company Of Biologists Ltd2015

Single-cell lipidomics reveals a role for cell-to-cell sphingolipid heterogeneity in fibroblast activation

Laura Capolupo

EPFL2021