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 |
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|---|---|---|---|---|---|---|---|---|
| Mouse |
NHP |
Humans |
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| 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.). |
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| NP2 Neuron Cluster |
Putative Cross-Species Cluster Equivalents |
|||||||
|---|---|---|---|---|---|---|---|---|
| Mouse |
NHP |
Human |
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| 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.). |
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| 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.). |
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