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Oligodendrocyte; axon-glia interaction; cross-species comparison; human; label-free proteomics; mouse; myelin sheath; neuroscience; scRNA-seq
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 expres-
sion and myelin protein composition can be informative when translating from mouse models to humans.
