Conservation and divergence of myelin proteome and oligodendrocyte transcriptome profiles between humans and mice
- Department of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, Germany
- Neuroproteomics Group, Department of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Germany
- Translational Neuroproteomics Group, Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Georg-August-University, Germany
- University of Amsterdam, Swammerdam Institute for Life Sciences, Brain Plasticity Group, Netherlands
- Neuroimmunology Group, Netherlands Institute for Neuroscience, Netherlands
- Electron Microscopy Unit, Max Planck Institute for Multidisciplinary Sciences, Germany
Figures
Figure 1 with 3 supplements
Proteome analysis of human central nervous system (CNS) myelin.
(a) Number and relative abundance of proteins identified in myelin purified from human normal-appearing white matter according to two data-independent acquisition (DIA) mass spectrometric modes (MSE,…
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Figure 1—source data 1
Label-free quantification of proteins in human central nervous system (CNS) myelin and white matter homogenate by two different data acquisition modes.
Identification and quantification data of detected myelin-associated and homogenate proteins. Tryptic peptides derived from two technical replicates (replicate digestion) per five biological replicates were analyzed by liquid chromatography–mass spectrometry (LC-MS) (10 runs per condition in total). Proteins (false discovery rate [FDR] < 1%; two peptides/protein) and peptides (FDR < 1%; ≥6 amino acids) were identified by database search against the UniProtKB/SwissProt mouse database using ProteinLynx Global Server (PLGS). Data were postprocessed with the software package ISOQuant to calculate absolute in-sample amounts for each detected protein based on the TOP3 approach. Reported abundance values are defined as the relative amount of each protein with respect to the sum over all detected proteins (ppm, parts per million [w/w] of total protein). Typical contaminant proteins like albumin, hemoglobins, keratins, and trypsin were filtered. Tables are sorted by description (column D) in alphabetical order.
- https://cdn.elifesciences.org/articles/77019/elife-77019-fig1-data1-v1.xlsx
Figure 1—figure supplement 1
Electron micrograph of the myelin-enriched fraction.
Representative electron micrograph of the myelin-enriched lightweight membrane fraction purified from the normal-appearing white matter of a human subject. Myelin sheaths are identified by their …
Figure 1—figure supplement 2
Pearson’s correlation for proteome analysis by MSE and UDMSE.
Clustered heatmap of Pearson’s correlation coefficients for protein abundance comparing myelin-enriched fraction and white matter homogenate by two data acquisition modes MSE in (a); UDMSE in (b). …
Figure 1—figure supplement 3
Heatmaps comparing the relative abundance of marker proteins in purified myelin versus white matter homogenate.
(a–h) Fold change (FC) comparing the abundance in myelin purified from human normal-appearing white matter with that in white matter homogenate according to the MSE dataset of marker proteins …
Figure 2 with 1 supplement
Comparison of the protein composition of human and mouse central nervous system (CNS) myelin.
(a) Silver-stained SDS-PAGE (0.9 μg protein load) of myelin purified from human normal-appearing white matter and C57Bl/6N mouse brains. Note that the band patterns are roughly comparable but not …
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Figure 2—source data 1
Labeled original immunoblots.
- https://cdn.elifesciences.org/articles/77019/elife-77019-fig2-data1-v1.xlsx
Figure 2—figure supplement 1
Detection of PMP2 in human central nervous system (CNS) myelin by immunoblot and immunohistochemistry.
(a) Immunoblot analysis of myelin purified from human normal-appearing white matter (CNS), C57Bl/6N mouse brains (CNS), and C57Bl/6N mouse sciatic nerves (peripheral nervous system [PNS]) using …
Figure 3 with 3 supplements
Cross-species scRNA-seq profile comparison of mature oligodendrocytes (MOL).
(a–c) Uniform manifold approximation and projection (UMAP) plot of the scRNA-seq profile of MOL integrated from previously established human (b) and mouse (c) datasets. In (a), cells contributed by …
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Figure 3—source data 1
Parameters applied for scRNA-seq individual dataset quality control and integrative analysis.
- https://cdn.elifesciences.org/articles/77019/elife-77019-fig3-data1-v1.docx
Figure 3—figure supplement 1
Integrated scRNA-seq profiles of the oligodendrocyte lineage in humans and mice.
(a, b) Uniform manifold approximation and projection (UMAP) plots of the scRNA-seq profiles of oligodendrocyte lineage cells integrated separately for humans (a) and mice (b) from previously …
Figure 3—figure supplement 2
Cross-species mature oligodendrocyte (MOL) transcriptome correlation.
Scatter plot comparing the van der Waerden (vdW) score-transformed average expression of 3000 integration features (i.e., genes) between human and mouse MOLs. Data points of 37 known myelin-related …
Figure 3—figure supplement 3
Comparisons of myelin proteome and mature oligodendrocyte (MOL) transcriptome.
van der Waerden (vdW) scores calculated from the mean abundance of integration features (n = 3000) in integrated scRNA-seq datasets of human (a, b) and mouse (c, d) MOL, and in the central nervous …
Figure 4 with 1 supplement
Human and mouse mature oligodendrocyte (MOL) subpopulation analysis.
(a) Uniform manifold approximation and projection (UMAP) plot showing five subpopulations of MOL identified upon integrating all human and mouse scRNA-seq datasets. (b) Bubble plot showing the top …
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Figure 4—source data 1
Model-based analysis of single-cell transcriptomics (MAST)-calculated marker genes from human and mouse integrated mature oligodendrocyte (MOL) subpopulations.
- https://cdn.elifesciences.org/articles/77019/elife-77019-fig4-data1-v1.csv
Figure 4—figure supplement 1
Gene Ontology (GO) term topics enriched per subpopulation.
GO terms of biological processes (small circles) were grouped as topics (large circles). Colors represent association with mature oligodendrocyte (MOL) clusters displayed in Figure 4. False …
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