Multi-omic identification of perineurial hyperplasia and lipid-associated nerve macrophages in human polyneuropathies
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 (365,7...
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Nature Portfolio
2025-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-62964-8 |
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| author | 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 Gerd Meyer zu Hörste |
| author_facet | 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 Gerd Meyer zu Hörste |
| author_sort | Michael Heming |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-73204e79bc814ca38b15f5b3fc0992aa |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-73204e79bc814ca38b15f5b3fc0992aa2025-08-24T11:38:03ZengNature PortfolioNature Communications2041-17232025-08-0116111410.1038/s41467-025-62964-8Multi-omic identification of perineurial hyperplasia and lipid-associated nerve macrophages in human polyneuropathiesMichael Heming0Anna-Lena Börsch1Jolien Wolbert2Christian Thomas3Anne K. Mausberg4Fabian Szepanowski5Bianca Eggert6I-Na Lu7Julia Tietz8Finja Dienhart9Maja Meschnark10Jan-Kolja Strecker11Michael Glatza12Carolina Thomas13Noemi Gmahl14Christine Dambietz15Michael Müther16Anne-Kathrin Uerschels17Kathy Keyvani18Jens Minnerup19Kathrin Doppler20Nurcan Üçeyler21Julieta Aprea22Andreas Dahl23Ruth Stassart24Robert Fledrich25Heinz Wiendl26Claudia Sommer27Mark Stettner28Gerd Meyer zu Hörste29Department of Neurology, University Hospital MünsterDepartment of Neurology, University Hospital MünsterDepartment of Neurology, University Hospital MünsterInstitute of Neuropathology, University Hospital MünsterDepartment of Neurology, Center for Translational Neuro- and Behavioural Sciences (C-TNBS), University Hospital EssenDepartment of Neurology, Center for Translational Neuro- and Behavioural Sciences (C-TNBS), University Hospital EssenDepartment of Neurology, Center for Translational Neuro- and Behavioural Sciences (C-TNBS), University Hospital EssenDepartment of Neurology, University Hospital MünsterDepartment of Neurology, University Hospital MünsterDepartment of Neurology, University Hospital MünsterDepartment of Neurology, University Hospital MünsterDepartment of Neurology, University Hospital Schleswig-HolsteinInstitute of Neuropathology, University Hospital MünsterPaul-Flechsig-Institute of Neuropathology, University Hospital LeipzigDepartment of Neurology, University Hospital MünsterDepartment of Neurology, University Hospital MünsterDepartment of Neurosurgery, University Hospital MünsterDepartment of Neurosurgery, University Hospital EssenDepartment of Neuropathology, University Hospital EssenDepartment of Neurology, University Hospital Schleswig-HolsteinDepartment of Neurology, University Hospital WürzburgDepartment of Neurology, University Hospital WürzburgDRESDEN-concept Genome Center, Center for Molecular and Cellular Bioengineering, Dresden University of TechnologyDRESDEN-concept Genome Center, Center for Molecular and Cellular Bioengineering, Dresden University of TechnologyPaul-Flechsig-Institute of Neuropathology, University Hospital LeipzigInstitute of Anatomy, University of LeipzigClinic of Neurology and Neurophysiology, University of FreiburgDepartment of Neurology, University Hospital WürzburgDepartment of Neurology, Center for Translational Neuro- and Behavioural Sciences (C-TNBS), University Hospital EssenDepartment of Neurology, University Hospital MünsterAbstract 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.https://doi.org/10.1038/s41467-025-62964-8 |
| spellingShingle | 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 Gerd Meyer zu Hörste Multi-omic identification of perineurial hyperplasia and lipid-associated nerve macrophages in human polyneuropathies Nature Communications |
| title | Multi-omic identification of perineurial hyperplasia and lipid-associated nerve macrophages in human polyneuropathies |
| title_full | Multi-omic identification of perineurial hyperplasia and lipid-associated nerve macrophages in human polyneuropathies |
| title_fullStr | Multi-omic identification of perineurial hyperplasia and lipid-associated nerve macrophages in human polyneuropathies |
| title_full_unstemmed | Multi-omic identification of perineurial hyperplasia and lipid-associated nerve macrophages in human polyneuropathies |
| title_short | Multi-omic identification of perineurial hyperplasia and lipid-associated nerve macrophages in human polyneuropathies |
| title_sort | multi omic identification of perineurial hyperplasia and lipid associated nerve macrophages in human polyneuropathies |
| url | https://doi.org/10.1038/s41467-025-62964-8 |
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