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3 Publications visible to you, out of a total of 3
Nonvesicular lipid transfer drives myelin growth in the central nervous system

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AbstractOligodendrocytes extend numerous cellular processes that wrap multiple times around axons to generate lipid-rich myelin sheaths. Myelin biogenesis requires an enormously productive biosynthetic … machinery for generating and delivering these large amounts of newly synthesized lipids. Yet, a complete understanding of this process remains elusive. Utilizing volume electron microscopy, we demonstrate that the oligodendroglial endoplasmic reticulum (ER) is enriched in developing myelin, extending into and making contact with the innermost myelin layer where growth occurs. We explore the possibility of transfer of lipids from the ER to myelin, and find that the glycolipid transfer protein (GLTP), implicated in nonvesicular lipid transport, is highly enriched in the growing myelin sheath. Mice with a specific knockout of Gltp in oligodendrocytes exhibit ER pathology, hypomyelination and a decrease in myelin glycolipid content. In summary, our results demonstrate a role for nonvesicular lipid transport in CNS myelin growth, revealing a cellular pathway in developmental myelination.

Authors: Jianping Wu, Georg Kislinger, Jerome Duschek, Ayşe Damla Durmaz, Benedikt Wefers, Ruoqing Feng, Karsten Nalbach, Wolfgang Wurst, Christian Behrends, Martina Schifferer, Mikael Simons

Date Published: 11th Nov 2024

Publication Type: Journal Article

Spatial Transcriptomics-correlated Electron Microscopy maps transcriptional and ultrastructural responses to brain injury

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Abstract Understanding the complexity of cellular function within a tissue necessitates the combination of multiple phenotypic readouts. Here, we developed a method that links spatially-resolved gene …ally-resolved gene expression of single cells with their ultrastructural morphology by integrating multiplexed error-robust fluorescence in situ hybridization (MERFISH) and large area volume electron microscopy (EM) on adjacent tissue sections. Using this method, we characterized in situ ultrastructural and transcriptional responses of glial cells and infiltrating T-cells after demyelinating brain injury in male mice. We identified a population of lipid-loaded “foamy” microglia located in the center of remyelinating lesion, as well as rare interferon-responsive microglia, oligodendrocytes, and astrocytes that co-localized with T-cells. We validated our findings using immunocytochemistry and lipid staining-coupled single-cell RNA sequencing. Finally, by integrating these datasets, we detected correlations between full-transcriptome gene expression and ultrastructural features of microglia. Our results offer an integrative view of the spatial, ultrastructural, and transcriptional reorganization of single cells after demyelinating brain injury.

Authors: Peter Androvic, Martina Schifferer, Katrin Perez Anderson, Ludovico Cantuti-Castelvetri, Hanyi Jiang, Hao Ji, Lu Liu, Garyfallia Gouna, Stefan A. Berghoff, Simon Besson-Girard, Johanna Knoferle, Mikael Simons, Ozgun Gokce

Date Published: 11th Jul 2023

Publication Type: Journal Article

Proteomic and lipidomic profiling of demyelinating lesions identifies fatty acids as modulators in lesion recovery

Abstract

Not specified

Authors: Horst Penkert, Alix Bertrand, Vini Tiwari, Stephan Breimann, Stephan A. Müller, Paul M. Jordan, Mathias J. Gerl, Christian Klose, Ludovico Cantuti-Castelvetri, Mar Bosch-Queralt, Ilya Levental, Stefan F. Lichtenthaler, Oliver Werz, Mikael Simons

Date Published: 1st Oct 2021

Publication Type: Journal Article

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