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. 2026 Jan 29;78(2):100121. doi: 10.1016/j.pharmr.2026.100121

Table 2.

Overview of key single-cell sequencing studies categorizing NP1-3 neurons in mice and putative correlates in NHP and human

NP1 Neuron Cluster
Putative Cross-Species Cluster Equivalents
Mouse
NHP
Humans
Study Usoskin et al., 201578 Zeisel et al., 201879 Sharma et al., 202080 Kupari et al., 202181 Nguyen et al., 202182 Tavares-Ferreira et al., 202283 Yu et al., 202484
Technology RNA single-cell sequencing RNA single-cell sequencing RNA single-cell sequencing RNA single-cell sequencing Single-nucleus transcriptomic human DRG Spatial transcriptomic analysis of human DRG Whole-soma scRNA-seq of human DRG (neuronal somata microdissection by laser)
Input Lumbar DRG (L-4-L6, 6-8 wk old, female + male).
622 neurons analyzed.
Cervical, thoracic & lumbar DRG (female & male). 2500 neurons analyzed. Cervical, thoracic & lumbar DRG. Macaque lumbar DRG (female & male).
Two independent data sets with 2518 and 1038 neurons.
Human lumbar DRG L4 & L5 (female & male donors). Nuclei from 1837 neurons. Human lumbar DRG L4 & L5 (female & male). Human thoracic T11 & 12 and lumbar DRG L2 - L5 (male & female). 1,066 neurons were used for analysis
Cluster name in study (+ frequencies if applicable) NP 1
Calculated Frequencies:
27,2% of all DRG neurons
73,96% of all NP neurons
PSNP 2 PSNP 3 MRGPRD+ polymodal
Nociceptors
Frequencies (RNA-FISH):
25% of cervical DRG neurons
23% of thoracic DRG neurons
24% of lumbar DRG neurons
NP 1 (cluster 8) Cluster H10 No corresponding cluster suggested Cluster 3: hNP1
Selection of enhanced transcripts Mrgprd, Lpar3, P2rx3, Gfra2, Gfra1, Ret, Trpa1, P2rx3, Nmb Gfra1, Gfra2, Mrgprd, Lpar3, P2rx3, P2Rx5, Ret (rather low), Mrgprx1, Mrgprx3, Mrgprx4, Adm, Il-31Ra, Sst, Osmr Gfra2, MrgprX1, Osmr, IL-31Ra, Hrh1, Nppb, Piezo2, Prdm8, Rergl N/A Mrgprd (only a few NP1 neurons), MrgprX1, Hrh1, Gfra2, IL-31Ra,Lpar3, Piezo2, Trpv-1, F2rl1, CysLTR2, Osmr, Nppb, Ednra
Annotations Zeisel et al. defined 2 NP1 subpopulations; it is unclear if this distinction is biologically relevant. NP1 & NP2 fibers between the mouse and NHP are less conserved, in comparison to NP3. H10 resembles murine NP1 in coclustering analyses, but H10 expresses murine NP2-related MRGPRX1, and murine NP3 restricts IL-31Ra. Expression of PIEZO2 suggests a role in mechanical itch. Two clusters, H10 & H11, were associated with itch sensation; however, an allocation to murine or NHP NP1 fibers was not suggested. Cell-type correlation analyses revealed good correspondence with Cluster H10 in the Nguyen et al. dataset.
A cross-species comparison reveals a good correlation with mouse (Sharma et al.) and macaque NP1 (Kupari et al.).
NP2 Neuron Cluster
Putative Cross-Species Cluster Equivalents
Mouse
NHP
Human
Study Usoskin et al., 201578 Zeisel et al., 201879 Sharma et al., 202080 Kupari et al., 202181 Nguyen et al., 202182 Tavares-Ferreira et al., 202283 Yu et al., 202484
Technology RNA single-cell sequencing RNA single-cell sequencing RNA single-cell sequencing RNA single-cell sequencing Single-nucleus transcriptomic human DRG Spatial transcriptomic analysis of human DRG Whole-soma scRNA-seq of human DRG (neuronal somata microdissection by laser)
Input Lumbar DRG (L-4-L6, 6-8 wk old) (female + male). 622 neurons analyzed. Cervical, thoracic & lumbar DRG (female & male). 2500 neurons analyzed. Cervical, thoracic & lumbar DRG. Macaque lumbar DRG (female & male). Two independent data sets with 2518 and 1038 neurons. Human lumbar DRG L4 & L5 (female & male donors). Nuclei from 1837 neurons. Human lumbar DRG L4 & L5 (male & female). 3952 barcodes overlapping with a single neuron Human thoracic T11 & 12 and lumbar DRG L2 - L5 (male & female). 1,066 neurons were used for analysis
Cluster name in study (+ frequencies if applicable) NP 2
Calculated Frequencies:
5,14 % of all DRG neurons
18,93 % of all NP neurons
PSNP 4 PSNP 5 CGRP θ
Frequencies (RNA-FISH):
8% of cervical DRG neurons
8% of thoracic DRG neurons
8% of lumbar DRG neurons
NP 2 (cluster 9) Partial coclustering with Cluster H10 & H11 No corresponding cluster suggested Cluster 4: hNP2
Selection of enhanced transcripts Mrgpra3, Trpa1, Trpv1 (for Zeisel data: PSNP5, but not PSNP4), Calca, Hrh1, P2rx3, Ret, Nmb, Osmr Gfra1, Mrgprx1, Mrgprx3, Mrgprx4, Pnoc, Chrna3, Ephb1, Gabrg3, Tpcn1, Calca, Ret, Sst, Osmr, Il-31Ra See Cluster H10 (human NP1 co-cluster) & Cluster H11 (human NP3 co-cluster) N/A Mrgprx4, MrgprX1, Hrh1, Hrh2, IL-31Ra, Trpv-1, CysLTR2, Osmr, Nppb
Annotations Zeisel et al. defined 2 NP2 subpopulations, and it is unclear if functional differences exist. NP1 & NP2 fibers between mouse and NHP were less conserved than NP3 between both species. Coclustering analyses revealed relations to H10 (NP1 correlate) and Cluster H11 (NP3 correlate). The chloroquine-sensitive MRGPRX1, for example, is found on Cluster H10, the equivalent of murine NP1. Two clusters, H10 and H11, were associated with itch sensation; however, an allocation/association between murine or NHP NP2 fibers was not suggested. Cell type correlation analyses revealed no correspondence to any of the clusters in the Nguyen et al. dataset.
A cross-species comparison reveals a good correlation with mouse (Sharma et al.) and macaque NP2 (Kupari et al.).
NP3 Neuron Cluster
Putative Cross-Species Cluster Equivalents
Mouse
NHP
Human
Study Usoskin et al., 201578 Zeisel et al., 201879 Sharma et al., 202080 Kupari et al., 202181 Nguyen et al., 202182 Tavares-Ferreira et al., 202283 Yu et al., 202484
Technology RNA single-cell sequencing RNA single-cell sequencing RNA single-cell sequencing RNA single-cell sequencing Single-nucleus transcriptomic human DRG Spatial transcriptomic analysis of human DRG Whole-soma scRNA-seq of human DRG (neuronal somata microdissection by laser)
Input Lumbar DRG (L-4-L6, 6-8 wk old) (female + male). 622 neurons analyzed. Cervical, thoracic & lumbar DRG (female & male). 2500 neurons analyzed. Cervical, thoracic & lumbar DRG. Macaque lumbar DRG (female & male). Two independent data sets with 2518 and 1038 neurons. Human lumbar DRG L4 & L5 (female & male donors). Nuclei from 1837 neurons. Human lumbar DRG L4 & L5 (male & female). 3952 barcodes overlapping with a single neuron Human thoracic T11 & 12 and lumbar DRG L2 - L5 (male & female). 1066 neurons were used for analysis
Cluster Name in study (+ frequencies if applicable) NP 3
Calculated Frequencies:
1,92 % of all DRG neurons
7,1 % of all NP neurons
PSNP6 Sst
Frequencies (RNA-FISH):
10 % of cervical DRG neurons
10 % of thoracic DRG neurons
9 % of lumbar DRG neurons
NP 7 (cluster 7) Cluster H11 No corresponding cluster suggested Cluster 5: hSST
Selection of enhanced transcripts Il-31Ra, Sst, Nppb, Osmr, S1pr1, Cystlr2, Gfra3, Jak1, Hrh1, Htr1f, Trpv1, Trpa1, Nts, P2rx3, Ret, Nmb, Ptafr Sst, Gfra3, Il-31Ra, Jak1, Osmr, S1pr1, App, Hrh1, Cxcr4, Tdrd1, Edn3, Gria1, Ret (rather low), Htr3b, Trpv-1 & Trpa1 (bot rather low) Osmr, Il-31Ra, Hrh1, Nppb, Sst, Cck, Jak1, Calca, Gfra3, Htr3a, Trpv-1 N/A Sst, IL-31Ra, Gfra3, Cck, Htr3a, Hrh1, Hrh2, Trpv-1, CysLTR2, Osmr, Nppb, Ednra
Annotations NP3 neurons between mouse and NHP are better conserved compared to Np1 and Np2 Two clusters, H10 + H11, were associated with itch sensation; however, an allocation/association between murine or NHP NP3 fibers and these 2 clusters was not suggested. Cell-type correlation analyses revealed good correspondence with Cluster H11 in the Nguyen et al. dataset.
A cross-species comparison reveals good correlation with mouse (Sharma et al.) and macaque NP3 (Kupari et al.).