Multi-omic identification of perineurial hyperplasia and lipid-associated nerve macrophages in human polyneuropathies

Michael Heming, Anna-Lena Börsch, Jolien Wolbert, Christian Thomas, Anne K. Mausberg, Fabian Szepanowski, Bianca Eggert, I-Na Lu, Julia Tietz, Finja Dienhart, Maja Meschnark, Jan-Kolja Strecker, Michael Glatza, Carolina Thomas, Noemi Gmahl, Christine Dambietz, Michael Müther, Anne-Kathrin Uerschels, Kathy Keyvani, Jens Minnerup, Kathrin Doppler, Nurcan Üçeyler, Julieta Aprea, Andreas Dahl, Ruth Stassart, Robert Fledrich, Heinz Wiendl, Claudia Sommer, Mark Stettner and Gerd Meyer zu Hörste ()
Additional contact information
Michael Heming: University Hospital Münster
Anna-Lena Börsch: University Hospital Münster
Jolien Wolbert: University Hospital Münster
Christian Thomas: University Hospital Münster
Anne K. Mausberg: University Hospital Essen
Fabian Szepanowski: University Hospital Essen
Bianca Eggert: University Hospital Essen
I-Na Lu: University Hospital Münster
Julia Tietz: University Hospital Münster
Finja Dienhart: University Hospital Münster
Maja Meschnark: University Hospital Münster
Jan-Kolja Strecker: University Hospital Schleswig-Holstein
Michael Glatza: University Hospital Münster
Carolina Thomas: University Hospital Leipzig
Noemi Gmahl: University Hospital Münster
Christine Dambietz: University Hospital Münster
Michael Müther: University Hospital Münster
Anne-Kathrin Uerschels: University Hospital Essen
Kathy Keyvani: University Hospital Essen
Jens Minnerup: University Hospital Schleswig-Holstein
Kathrin Doppler: University Hospital Würzburg
Nurcan Üçeyler: University Hospital Würzburg
Julieta Aprea: Dresden University of Technology
Andreas Dahl: Dresden University of Technology
Ruth Stassart: University Hospital Leipzig
Robert Fledrich: University of Leipzig
Heinz Wiendl: University of Freiburg
Claudia Sommer: University Hospital Würzburg
Mark Stettner: University Hospital Essen
Gerd Meyer zu Hörste: University Hospital Münster

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Diseases affecting multiple peripheral nerves, termed polyneuropathies (PNPs), are common, mechanistically heterogeneous, and their causes are challenging to identify. Here, we integrated single-nucleus transcriptomics of peripheral nerves from 33 human PNP patients and four controls (365,708 nuclei) with subcellular spatial transcriptomics. We identified nerve cell type markers and uncovered unexpected heterogeneity of perineurial cells. PNPs shared a loss of myelinating and an increase in repair Schwann cells and endoneurial lipid-phagocytizing macrophages. Transcriptional changes affected multiple cells outside of the endoneurium across PNPs, suggesting PNPs as ‘pan-nerve diseases’. Spatially, PNPs—particularly those mediated by autoimmunity—exhibited focal perineurial hyperplasia and increased expression of CXCL14, identified as perineurial cell marker. Multi-omic characterization of human nerve biopsies thus identified novel mechanisms in PNPs with diagnostic potential.

Date: 2025
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DOI: 10.1038/s41467-025-62964-8

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