Conservation and divergence of myelin proteome and oligodendrocyte transcriptome profiles between humans and mice

Vasiliki-Ilya Gargareta, Josefine Reuschenbach, Sophie B Siems, Ting Sun, Lars Piepkorn, Carolina Mangana, Erik Späte, Sandra Goebbels, Inge Huitinga, Wiebke Möbius, Klaus-Armin Nave, Olaf Jahn, Hauke B Werner

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Abstract

Human myelin disorders are commonly studied in mouse models. Since both clades evolutionarily diverged approximately 85 million years ago, it is critical to know to what extent the myelin protein composition has remained similar. Here, we use quantitative proteomics to analyze myelin purified from human white matter and find that the relative abundance of the structural myelin proteins PLP, MBP, CNP, and SEPTIN8 correlates well with that in C57Bl/6N mice. Conversely, multiple other proteins were identified exclusively or predominantly in human or mouse myelin. This is exemplified by peripheral myelin protein 2 (PMP2), which was specific to human central nervous system myelin, while tetraspanin-2 (TSPAN2) and connexin-29 (CX29/GJC3) were confined to mouse myelin. Assessing published scRNA-seq-datasets, human and mouse oligodendrocytes display well-correlating transcriptome profiles but divergent expression of distinct genes, including Pmp2, Tspan2, and Gjc3. A searchable web interface is accessible via www.mpinat.mpg.de/myelin. Species-dependent diversity of oligodendroglial mRNA expression and myelin protein composition can be informative when translating from mouse models to humans.

Original languageEnglish
Article numbere77019
JournaleLife
Volume11
DOIs
Publication statusPublished - 11 May 2022

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