Gerd Meyer zu Hörste We are excited to present a first large-scale (365,708 nuclei) single cell atlas of human peripheral nerves combined with subcelullar spatial transcriptomics (#Xenium) biorxiv.org/content/10.110… Explore yourself at : pns-atlas.mzhlab.com 🧵A tweetorial: 1/11

Exciting news! Our new paper is published at Annals of Neurology! Check it out to see how large-scale CSF and blood flow cytometry can reveal disease clusters to improve diagnosis and understanding doi.org/10.1002/ana.27…

So proud of this collaborative work! Thanks to all involved, including Claudia Cantoni Brian Edelson Maxim Artyomov Gerd Meyer zu Hörste Joe Sabatino

We are looking for a leader of our new spatial #biology core facility. Join us if you are interested to work with mulitplexed immunohistochemistry, spatial transcriptomics, and mass spec imaging in the fields of #inflammation, #cancer, and #Neuroscience. jobs-sf.ukmuenster.de/job/UKM-Postdo…

Thrilled to announce that our latest work is now online in Genome Medicine! We identified a mechanism driving ICANS following CAR T cell treatment. doi.org/10.1186/s13073…

Our paper was just published in Nature Communications. First single‑nucleus atlas of human sural nerves in health and disease. Identified lipid‑phagocytosing macrophages, and focal perineurial hyperplasia especially in immune polyneuropathies. rdcu.be/eB2Dg

Very proud that our human PNS atlas is finally published in Nature Communications. We found perineurial hyperplasia and lipid-associated nerve macrophages in #polyneuropathies. Explore: pns-atlas.mzhlab.com A tweetorial 1/13 doi.org/10.1038/s41467…

2/13 Polyneuropathies (PNP) are among the most common neurological diseases (~4%, but the underlying causes remain unclear in many patients (~20-30%). We used state of the art single cell technologies to better characterize sural nerves in health and disease.

3/13 We combined single nuclei sequencing of 33 human polyneuropathy patients and four controls (365,708 nuclei) with subcellular spatial transcriptomics (#Xenium).

4/13 Single nuclei sequencing dissected cell populations in the sural nerve in great detail, replicating and extending cell populations identified in single cell rodent studies. Interestingly, we identified transcriptionally heterogeneous perineurial fibroblasts.

5/13 We identified novel and human-specific nerve cell type markers using snRNA-seq, which were validated using spatial transcriptomics

6/13 Integrating spatial transcriptomics with snRNA-seq provided an unbiased histological annotation of peripheral nerve cells.

7/13 Human peripheral nerves contained complex immune cells, including a plethora of myeloid cell populations. Macrophage clusters exhibited an endoneurial to epineurial gradient, previously described in rodents.

9/13 LAM markers (SPP1/osteopontin, PLIN2, CD36, FABP5) colocalized histologically with myelin and BODIPY (labels neutral lipids). LAM thus likely has myelin-phagocytizing capacity.

10/13 immune, repairSC and periC3 cluster also correlated with clinical disease severity (INCAT score) and myelin thickness (g-ratio). (using CNA Ilya Korsunsky

11/13 Transcriptional changes affected multiple cells outside of the endoneurium across PNPs, suggesting PNPs as pan-nerve diseases (using miloDE from MarioniLab )

12/13 PNPs showed previously unknown perineurial hyperplasia and fibrotic dispersion and this was most pronounced in immune-mediated PNPs.

13/13 Validated in a larger cohort (370 fascicles; 18 CTRL, 12 CIDP): manual perineurium measurements. Linear mixed model (age+sex fixed, center/sample random) showed perineurial area & perimeter increased in CIDP.

Linking people who were involved or who might be interested in reading this: Gerd Meyer zu Hörste @borschanna Jolien Wolbert Christian thomas Claudia L. Sommer Peripheral Nerve Society (PNS) @LuiseAppeltshauser Ming "Tommy" Tang Diana Tavares Ferreira

Gerd Meyer zu Hörste Anna-Lena Börsch Jolien Wolbert Christian thomas Claudia L. Sommer Peripheral Nerve Society (PNS) Ming "Tommy" Tang Diana Tavares Ferreira Michael Müther Luise Appeltshauser MD MSc Robert Fledrich Heinz Wiendl