Table V.
Neuron cluster based on transcriptional analysis and predicted function | Markers | Subtypes | Subtype markers | Classification of DRGs based on size, myelination, and markers——-Small neurons——Large neurons |
Highly expressed TR channel types per cluster subtype | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|
PEPPeptidergic (myelinated+unmyelinated) | NPNonpeptidergic (unmyelinated) | TH (unmyelin-ated)C-LTMRsTh | NF(myelinated) | ||||||||
Tac1 | Calca | IB4 | P2 × 3r | Plxnc1 | Nefh | Ldhb | |||||
Small fiberneurons | |||||||||||
C1 | Gal | C1–1 | Asic3high | Trpv1high | |||||||
MHN | Adcyapl | Cldn9 | Trpm8hgh | ||||||||
C1–2 |
Zcchcl2
Sstr2 |
Trpm3high | |||||||||
C2 | Nppb | 02–1 | Pvalb+ | Trpv2high | |||||||
MHN (MI, IS) | Il31ra | S100b− | |||||||||
C2–2 |
Pva1b−
S100b+ |
Trpm3high | |||||||||
C3 | Th | – | Trpv2high | ||||||||
C-LTMR | Zfp521 | Trpv4high | |||||||||
C4 | Mrgpra3 | C4–1 |
Mrgprb4−
Ptpn6− |
||||||||
MHN (IS) | Rspo1 | C4–2 |
Mrgprb4+
Ptpn6+ |
||||||||
C5 | Mrgprd (highly expressed) | C5–1 |
Gfra3+
Sstr2+ |
Trpm3high | |||||||
MHN (IS) | Prkcq, Lpar3 | C5–2 |
Gfra3+
Sstr2+ |
Trpv2high | |||||||
C6 | Mrgprd (moderately expressed) S100b | C6–1 |
Ntrk1+
Prkcqlow |
||||||||
MHN | C6–2 |
Ntrk1
Prkcqhigh |
Trpv2high | ||||||||
Large fiber neurons | |||||||||||
C7 | Nxph1, Wnt7a, S100b | – | – | ||||||||
MHN (MS) | |||||||||||
C8 | Trappc31, Cgn11, S100b | C8–1 | Ntrk3high | Trpm8high | |||||||
MR | Htr1dhigh | ||||||||||
C8–2 |
Ntrk1high
Htr3ahigh |
Trpm8high | |||||||||
C9 | Baiap2l1, Cadps2, S100b | C9–1 |
Asic3−
Cgnl1low |
||||||||
MN | C9–2 |
Asic3+
Cgnl1high |
|||||||||
C10 | Gal, | – | – | Trpv2high | |||||||
MR or P | Rspo1 | – | – |
Trpv1high
Trpa1high Trpm3high |
Gray-filled squares indicate highly expressed markers per cluster.
Abbreviations: Adcyap1, pituitary adenylate cyclase-activating polypeptide 1; Asic3, acid sensing ion channel subunit 3; Baiap2l1, brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1; Cadps2, calcium-dependent secretion activator 2; Calca, calcitonin-related polypeptide-α; Cgnl1, cingulin-like 1; C-LTMR, C fiber low-threshold mechanoreceptor; Cldn9, claudin 9; Gal, galanin; Gfra3, GDNF family receptor-α3; Htr1d, 5-hydroxytryptamine receptor 1D; Il31ra, interleukin-31 receptor A; IS, itch-sensitive; Ldhb, lactate dehydrogenase B; Lpar3, lysophosphatidic acid receptor 3; MHN, mechanoheat nociceptor; MI, mechanically insensitive; MN, mechanical nociceptor; MR, mechanoreceptor; Mrgpra3, Mas-related G-protein coupled receptor member A3; Mrgprb4, Mas-related G-protein coupled receptor member B4; Mrgprd, Mas-related G-protein coupled receptor member D; MS, mechanically sensitive; Nefh, neurofilament heavy; NF, neurofilament-positive; NP, nonpeptidergic; Nppb, natriuretic peptide B; Ntrk1, neurotrophic receptor tyrosine kinase 1; Nxph1, neurexophilin 1; P, proprioceptor; Plxnc1, plexin C1; Ptpn6, protein tyrosine phosphatase non receptor type 6; Prkcq, protein kinase c theta; Pvalb, parvalbumin; P2 × 3r, purinergic receptor P2 × 3; PEP, peptidergic; Rspo1, R-spondin 1; Sstr2, somatostatin receptor 2; S100b, S100 calcium binding protein B; Tac1, tachykinin precursor 1; TH/Th, tyrosine hydroxylase; Trappc3l, trafficking protein particle complex subunit 3-like protein; Trpm, transient receptor potential melastatin; Trpv, transient receptor potential cation channel; Wnt7a, Wnt family member 7A; Zcchc12, zinc finger CCHC domain-containing protein 12; Zfp521, zinc finger protein 521.