Multi-omic identification of perineurial hyperplasia and lipid-associated nerve macrophages in human polyneuropathies
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.
Article Details
Authors (30)
Michael Heming
Department of Neurology, University Hospital Münster
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
Institute for Neurology and Neurophysiology, Faculty of Medicine, University of Freiburg
Claudia Sommer
Mark Stettner
Gerd Meyer zu Hörste
Department of Neurology, University Hospital Münster