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.
August 24, 2025 at 1:08 PM
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.
12/13
PNPs showed previously unknown perineurial hyperplasia and fibrotic dispersion and this was most pronounced in immune-mediated PNPs.
PNPs showed previously unknown perineurial hyperplasia and fibrotic dispersion and this was most pronounced in immune-mediated PNPs.
August 24, 2025 at 1:08 PM
12/13
PNPs showed previously unknown perineurial hyperplasia and fibrotic dispersion and this was most pronounced in immune-mediated PNPs.
PNPs showed previously unknown perineurial hyperplasia and fibrotic dispersion and this was most pronounced in immune-mediated PNPs.
11/13 Transcriptional changes affected multiple cells outside of the endoneurium across PNPs, suggesting PNPs as pan-nerve diseases (using miloDE)
August 24, 2025 at 1:08 PM
11/13 Transcriptional changes affected multiple cells outside of the endoneurium across PNPs, suggesting PNPs as pan-nerve diseases (using miloDE)
10/13 immune, repairSC and periC3 cluster also correlated with clinical disease severity (INCAT score) and myelin thickness (g-ratio). (using CNA @ilyakorsunsky.bsky.social
August 24, 2025 at 1:08 PM
10/13 immune, repairSC and periC3 cluster also correlated with clinical disease severity (INCAT score) and myelin thickness (g-ratio). (using CNA @ilyakorsunsky.bsky.social
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.
August 24, 2025 at 1:08 PM
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.
8/13 PNPs shared an increase in endoneurial lipid-associated macrophages (LAM).
August 24, 2025 at 1:08 PM
8/13 PNPs shared an increase in endoneurial lipid-associated macrophages (LAM).
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.
August 24, 2025 at 1:08 PM
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.
6/13 Integrating spatial transcriptomics with snRNA-seq provided an unbiased histological annotation of peripheral nerve cells.
August 24, 2025 at 1:08 PM
6/13 Integrating spatial transcriptomics with snRNA-seq provided an unbiased histological annotation of peripheral nerve cells.
5/13 We identified novel and human-specific nerve cell type markers using snRNA-seq, which were validated using spatial transcriptomics
August 24, 2025 at 1:08 PM
5/13 We identified novel and human-specific nerve cell type markers using snRNA-seq, which were validated using spatial transcriptomics
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.
August 24, 2025 at 1:08 PM
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.
Very proud that our human PNS atlas is finally published in @natcomms.nature.com We found perineurial hyperplasia and lipid-associated nerve macrophages in #polyneuropathies.
Explore: pns-atlas.mzhlab.com
A tweetorial 1/13
doi.org/10.1038/s414...
Explore: pns-atlas.mzhlab.com
A tweetorial 1/13
doi.org/10.1038/s414...
August 24, 2025 at 1:08 PM
Very proud that our human PNS atlas is finally published in @natcomms.nature.com We found perineurial hyperplasia and lipid-associated nerve macrophages in #polyneuropathies.
Explore: pns-atlas.mzhlab.com
A tweetorial 1/13
doi.org/10.1038/s414...
Explore: pns-atlas.mzhlab.com
A tweetorial 1/13
doi.org/10.1038/s414...
15/16
#Dementia patients in the neurodegenerative cluster showed more severe disease progression. CSF cell analysis may thus help predict the progression of dementia.
#Dementia patients in the neurodegenerative cluster showed more severe disease progression. CSF cell analysis may thus help predict the progression of dementia.
December 12, 2024 at 9:33 PM
15/16
#Dementia patients in the neurodegenerative cluster showed more severe disease progression. CSF cell analysis may thus help predict the progression of dementia.
#Dementia patients in the neurodegenerative cluster showed more severe disease progression. CSF cell analysis may thus help predict the progression of dementia.
December 12, 2024 at 9:33 PM
13/16
Interestingly, #MS patients were more likely to have a #progressiveMS when assigned to the neurodegenerative cluster.
Interestingly, #MS patients were more likely to have a #progressiveMS when assigned to the neurodegenerative cluster.
December 12, 2024 at 9:33 PM
13/16
Interestingly, #MS patients were more likely to have a #progressiveMS when assigned to the neurodegenerative cluster.
Interestingly, #MS patients were more likely to have a #progressiveMS when assigned to the neurodegenerative cluster.
12/16
We further used datathin to split our data (with cluster annotations). By training an #XGBoost model on the train set and evaluating on the test, we could validate our clustering. Additionally, we used a second cohort of 3,201 patients to validate our disease clusters.
We further used datathin to split our data (with cluster annotations). By training an #XGBoost model on the train set and evaluating on the test, we could validate our clustering. Additionally, we used a second cohort of 3,201 patients to validate our disease clusters.
December 12, 2024 at 9:33 PM
12/16
We further used datathin to split our data (with cluster annotations). By training an #XGBoost model on the train set and evaluating on the test, we could validate our clustering. Additionally, we used a second cohort of 3,201 patients to validate our disease clusters.
We further used datathin to split our data (with cluster annotations). By training an #XGBoost model on the train set and evaluating on the test, we could validate our clustering. Additionally, we used a second cohort of 3,201 patients to validate our disease clusters.
11/16
To validate the number of clusters, we used datathin method, which splits a random variable into an independent training and test set. @tommytang.bsky.social www.jmlr.org/papers/v25/2...
To validate the number of clusters, we used datathin method, which splits a random variable into an independent training and test set. @tommytang.bsky.social www.jmlr.org/papers/v25/2...
December 12, 2024 at 9:33 PM
11/16
To validate the number of clusters, we used datathin method, which splits a random variable into an independent training and test set. @tommytang.bsky.social www.jmlr.org/papers/v25/2...
To validate the number of clusters, we used datathin method, which splits a random variable into an independent training and test set. @tommytang.bsky.social www.jmlr.org/papers/v25/2...
10/16
Technical site note: SoupX worked great in this context by identifying top features (diseases) per cluster via TF-IDF (much better than Seurat wilcox test) @tommytang.bsky.social
Technical site note: SoupX worked great in this context by identifying top features (diseases) per cluster via TF-IDF (much better than Seurat wilcox test) @tommytang.bsky.social
December 12, 2024 at 9:33 PM
10/16
Technical site note: SoupX worked great in this context by identifying top features (diseases) per cluster via TF-IDF (much better than Seurat wilcox test) @tommytang.bsky.social
Technical site note: SoupX worked great in this context by identifying top features (diseases) per cluster via TF-IDF (much better than Seurat wilcox test) @tommytang.bsky.social
9/16
Classifying all diseases solely based on the CSF/blood parameters in 8,790 patients resulted in clusters of 4 disease categories: healthy, autoimmune, meningoencephalitis, and neurodegenerative.
Classifying all diseases solely based on the CSF/blood parameters in 8,790 patients resulted in clusters of 4 disease categories: healthy, autoimmune, meningoencephalitis, and neurodegenerative.
December 12, 2024 at 9:33 PM
9/16
Classifying all diseases solely based on the CSF/blood parameters in 8,790 patients resulted in clusters of 4 disease categories: healthy, autoimmune, meningoencephalitis, and neurodegenerative.
Classifying all diseases solely based on the CSF/blood parameters in 8,790 patients resulted in clusters of 4 disease categories: healthy, autoimmune, meningoencephalitis, and neurodegenerative.
6/16
We next trained an #XGBoost model on 588 somatoform patients and found that the prediction on the remaining 200 patients showed a strong correlation with true biological age (Pearson r = 0.71).
We next trained an #XGBoost model on 588 somatoform patients and found that the prediction on the remaining 200 patients showed a strong correlation with true biological age (Pearson r = 0.71).
December 12, 2024 at 9:33 PM
6/16
We next trained an #XGBoost model on 588 somatoform patients and found that the prediction on the remaining 200 patients showed a strong correlation with true biological age (Pearson r = 0.71).
We next trained an #XGBoost model on 588 somatoform patients and found that the prediction on the remaining 200 patients showed a strong correlation with true biological age (Pearson r = 0.71).
5/16
Age primarily affected #Tcells in #CSF and blood, which became activated with age. Interestingly, #CD8Tcells increased in #CSF with age but decreased in blood, suggesting that age-related changes are partially compartment-specific.
Age primarily affected #Tcells in #CSF and blood, which became activated with age. Interestingly, #CD8Tcells increased in #CSF with age but decreased in blood, suggesting that age-related changes are partially compartment-specific.
December 12, 2024 at 9:33 PM
5/16
Age primarily affected #Tcells in #CSF and blood, which became activated with age. Interestingly, #CD8Tcells increased in #CSF with age but decreased in blood, suggesting that age-related changes are partially compartment-specific.
Age primarily affected #Tcells in #CSF and blood, which became activated with age. Interestingly, #CD8Tcells increased in #CSF with age but decreased in blood, suggesting that age-related changes are partially compartment-specific.
4/16
In a subcohort of 788 somatoform patients, we found that #Tcells in blood were increased in females, while albumin, protein, IgG, IgA, and IgM ratios were increased in males.
December 12, 2024 at 9:33 PM
4/16
In a subcohort of 788 somatoform patients, we found that #Tcells in blood were increased in females, while albumin, protein, IgG, IgA, and IgM ratios were increased in males.
@mzhlab.bsky.social I am proud to share our manuscript published in @ANA_journals today. doi.org/10.1002/ana....
We used data-driven approaches to analyze paired #CSF and blood #FlowCytometry of 8,790 (discovery) + 3,201 (validation) patients
A #tweetorial 1/16
We used data-driven approaches to analyze paired #CSF and blood #FlowCytometry of 8,790 (discovery) + 3,201 (validation) patients
A #tweetorial 1/16
December 12, 2024 at 9:33 PM
@mzhlab.bsky.social I am proud to share our manuscript published in @ANA_journals today. doi.org/10.1002/ana....
We used data-driven approaches to analyze paired #CSF and blood #FlowCytometry of 8,790 (discovery) + 3,201 (validation) patients
A #tweetorial 1/16
We used data-driven approaches to analyze paired #CSF and blood #FlowCytometry of 8,790 (discovery) + 3,201 (validation) patients
A #tweetorial 1/16
11/11 PNPs showed previously unknown perineurial hyperplasia and fiibrotic dispersion and this was most pronounced in immune-mediated PNPs. Thanks for reading.
December 10, 2024 at 10:20 PM
11/11 PNPs showed previously unknown perineurial hyperplasia and fiibrotic dispersion and this was most pronounced in immune-mediated PNPs. Thanks for reading.
10/11 Transcriptional changes affected multiple cells outside of the endoneirum across PNPs, suggesting PNPs as pan-nerve diseases (using miloDE from MarioniLab)
December 10, 2024 at 10:20 PM
10/11 Transcriptional changes affected multiple cells outside of the endoneirum across PNPs, suggesting PNPs as pan-nerve diseases (using miloDE from MarioniLab)
9/11 In addition, these clusters also correlated with clinical disease severity (INCAT score) and myelin thickness (g-ratio). (using CNA from @ilyakorsunsky.bsky.social
December 10, 2024 at 10:20 PM
9/11 In addition, these clusters also correlated with clinical disease severity (INCAT score) and myelin thickness (g-ratio). (using CNA from @ilyakorsunsky.bsky.social