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SHOX2 interneurons? Simply listing the differentially expressed genes above. TPH2 relates to the biosynthesis of serotonin. DDC encodes the dopa decarboxylase enzyme which synthesizes amine neurotransmitters, such as dopamine, norepinephrine, serotonin, and trace amines.
Note: these cells being MidVentral and expressing VSX2 probably overlap with the cells from this study on the restoration of walking after paralysis: https://www.nature.com/articles/s41586-022-05385-7
I suggest calling this Group GRPR:LMO3.
Overlap with the Exc-LMO3 neurons of Arokiaraj et al. We've seen LMO3 hold up as a specific marker for these cells in mouse, rat, macaque, and pig. In mouse specifically, this has a lot of overlap with substance P (TAC1)+ neurons, of big interest to pain field. But we didn't find TAC1 gene as conserved specificity in macaque or pig. https://pubmed.ncbi.nlm.nih.gov/32634530/ https://www.cell.com/cell-reports/pdf/S2211-1247(24)01227-0.pdf
This cluster also expresses NPY and LHX1/5. I hypothesize this cluster represents the deep dorsal horn NPY neurons based on the expression of Neurod6 (our mice Xenium data) and DRD5 (see https://www.jneurosci.org/content/38/2/379) which are expressed in deep dorsal horn in mice.
Suggested name: DH MAF:PVALB Glut laminar III Excitatory MAF previously described in mouse, macaque, human, pig (unpublished, can share). Also high PVALB (seen by us in Xenium, seen here in your data). Unpublished but can share results: High specificity of MAF transcription factor motifs found in open chromatin of these DH MAF+ neurons. Note: part of CCK+ class of neurons, but CCK expressed in other groups https://www.cell.com/cell-reports/pdf/S2211-1247(24)01227-0.pdf https://pmc.ncbi.nlm.nih.gov/articles/PMC10157139/#:~:text=j.celrep.2023.112295-,c%2DMaf%2Dpositive%20spinal%20cord%20neurons%20are%20critical%20elements%20of,for%20mechanical%20hypersensitivity%20in%20neuropathy https://www.sciencedirect.com/science/article/pii/S0896627320308230
Suggested naming: SDH PDYN:GAL GABA Previously described PDYN+ inhibitory neurons and cross-species marker in macaque, pig (although GABA-Dorsal-6 also expresses PDYN). Gal+ inhibitory neurons are involved in the morphine mechanism of antinociception: https://www.science.org/doi/full/10.1126/science.ado6593 Galanin-mediated control of pain: https://www.pnas.org/doi/pdf/10.1073/pnas.89.8.3334 PDYN conservation in macaque: https://www.cell.com/cell-reports/pdf/S2211-1247(24)01227-0.pdf
Suggested name: DH PDYN GLUT Reasoning: previously described excitatory PDYN neurons in mouse (a few studies), and conserved specificity in macaque, human, pig. Although transcriptomically like the MidVent cells, it's located mostly in laminae I-IV hence suggested DH name. https://pmc.ncbi.nlm.nih.gov/articles/PMC3438856/ https://pubmed.ncbi.nlm.nih.gov/33045156/ https://www.mdpi.com/1422-0067/22/5/2297
This cluster is likely to be the conserved NPY interneuron population in the dorsal horn across species. Expression of LHX1 is required for NPY neuron development (see https://www.sciencedirect.com/science/article/pii/S001216060801110X?via%3Dihub#aep-abstract-id18). Also the presence of SKOR2 suggest this may be the SDH (I-II) NPY interneuron subpopulation, but this will need to be confirmed with spatial transcriptomics. GABA-Dorsal 1 also expresses NPY and LHX1, but I hypothesize that GABA-Dorsal 1 represents the deep dorsal horn NPY population.
Suggested name: SDH NPY GABA Reasoning: previously described NPY-expressing inhibitory dorsal subpopulation cross-species specific (including pig, in preparation). Could add a second marker since NPY seems spread out https://elifesciences.org/reviewed-preprints/86633 https://pmc.ncbi.nlm.nih.gov/articles/PMC3858808/ https://www.cell.com/cell-reports/pdf/S2211-1247(24)01227-0.pdf
Suggested name: SDH PRKCG:NTS Glut Reasoning: Gluta-Dorsal-2 and Gluta-Dorsal-3 express Prkc-gamma a useful spatial landmark for lamina II/III boundary (at least in mouse). neurotensin (NTS) is most specific to Gluta-dorsal-3 and is a cross-species maker of this group in mouse,macaque,human,pig. neurotensin as a chemical has antinociceptive properties https://www.cell.com/cell-reports/pdf/S2211-1247(24)01227-0.pdf https://insight.jci.org/articles/view/169554 https://pmc.ncbi.nlm.nih.gov/articles/PMC8740200/
I suggest this group to be called GRPR:SKOR2.
These seem to correspond to Exc-SKOR2 neurons in Arokiaraj et al but SKOR2 marker isn't great here. Also one of the groups expressing GRPR, but in our macaque snRNA-seq we weren't confident that GRPR was conserved. Becky Seal and Sam Noh have some interesting behavioral findings on a subset of GRPR+ neurons in mouse. Some previous research below: https://pmc.ncbi.nlm.nih.gov/articles/PMC9756441/ https://www.pnas.org/doi/10.1073/pnas.1905658116
We called these Exc-BNC2 in Arokiaraj et al, but although BNC2 is species-conserved specific, is also highly expressed in your gluta-Dorsal-1, which we've seen consistently as well (in what we called Exc-MAFA). No particular suggestion for naming, but BNC2 might be helpful
In Arokiaraj et al we had Gluta-Dorsal-6 and Gluta-Dorsal-7 lumped together and called Exc-NMUR2. NMUR2 has been a species conserved marker in mouse, rat, macaque, pig. NMUR2 as marker and as receptor of NMU has been interesting to pain field. Mostly Lamina II outer https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=92b570bce5a233d02d7ca2e27ab6f571e20c0245 https://journals.lww.com/pain/fulltext/2019/02000/morphological_and_functional_properties.18.aspx
overlap with the Exc-TAC3 neurons in Arokiaraj et al. No specific suggestions, may consider lumping with Gluta-Dorsal-11 unless you find really unique differences. Neurokinin B (derived from TAC3) is previously reported as an important neuropeptide in dorsal horn https://www.nature.com/articles/nrn2947#:~:text=Key%20Points,information%20to%20several%20brain%20areas. https://pubmed.ncbi.nlm.nih.gov/16446041/
This cluster may be another NPY interneuron subtype. This cluster has relatively higher co-expression of NXPH2. Perhaps this can be NPY:NXPH2 group.
Suggested naming: SDH NMU:? Glut Reasoning: Neuromedin U (NMU) previously described as species-conserved marker for this group in mouse, human, macaque, pig, rat. Some NMU expression in other clusters but comparably not much. Closely related to your adjacent group which expresses some NMU, may want to lump them together but not sure. https://www.nature.com/articles/s41593-018-0141-1 https://www.cell.com/cell-reports/pdf/S2211-1247(24)01227-0.pdf Note also NMU the chemical has behavioral effects including hyperalgesia: https://pmc.ncbi.nlm.nih.gov/articles/PMC1665182/
see gluta-dorsal-6 feedback
Suggested name: SDH PVALB GABA (if PVALB is conserved enough in macaque). Reasoning: Inhibitory superficial dorsal PVALB neurons previously described as important neuron group. Note: some excitatory neurons have high PVALB expression, and some deeper inhibitory neurons express PVALB, but the naming as suggested differentiates between them. Referred to as Inh-CACNA2D3 in Arokiaraj, et al, but we had trouble measuring PVALB in snRNA-seq. If you have good enough signal in macaque, it's probably a better marker https://journals.lww.com/pain/fulltext/2022/03000/diversity_of_inhibitory_and_excitatory_parvalbumin.23.aspx https://pmc.ncbi.nlm.nih.gov/articles/PMC3858808/
these correspond to what we called Exc-MAFA in Arokiaraj et al and have MAFA expression here as well. This is a cross-species marker, but MAFA is also high in Gluta-Dorsal-4, so it may not be ideal for use in naming. We saw these neurons mostly in lamina II
Suggested naming: SDH PRKCG:TRH Glut Reasoning: Part of Prkc-gamma cells forming lamina II/III boundary. We called this group Exc-SNTB1 in Arokiaraj et al, and SNTB1 is a species-conserved marker. That said, thyrotropin releasing hormone (TRH) is really specific for these cells! and Prkcg+TRH+ neurons have been previously studied by others, apparently even in 1986 https://pubmed.ncbi.nlm.nih.gov/3096489/ https://onlinelibrary.wiley.com/doi/full/10.1002/cne.24657
Suggested name: SDH CALB2:TAC1 GABA (if these genes are conserved enough in macaque) Reasoning: previously described calretinin(CALB2)-expressing inhibitory dorsal subpopulation ( though most high CALB2 cells glutametergic). One other marker gene (possibly TAC1, previously used by field) could differentiate this group from GABA-Dorsal-10 Note: We called these cells Inh-NXPH1 in Arokiaraj et al (see figure 4 for laminae II arrangement and marker genes). But NXPH1 isn't a great marker https://www.nature.com/articles/s41598-023-38605-9 https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/JP270855 https://pubmed.ncbi.nlm.nih.gov/30553791/
This group seems to have some cells overlapping with midventral cells. Seems wrong. As for majority of the cluster, inhibitory and expresses PDYN, a cross-species marker. Galanin-negative. No specific suggestion for another marker https://pmc.ncbi.nlm.nih.gov/articles/PMC7744314/#:~:text=Moreover%2C%20although%20the%20majority%20of,neurons%20following%20neonatal%20tissue%20damage.
Suggested name: SDH CALB2:RXFP2 GABA (if these genes are conserved enough in macaque) Reasoning: previously described calretinin(CALB2)-expressing inhibitory dorsal subpopulation ( though most high CALB2 cells glutametergic). One other marker gene (possibly RXFP2) could differentiate this group from GABA-Dorsal-3 https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/JP270855 https://pubmed.ncbi.nlm.nih.gov/30553791/
Suggested naming: SDH PDYN:? GABA One of three inhibitory groups expressing PDYN, a cross-species marker. (See Gaba-Dorsal-8 suggestion). Galanin-negative. No specific suggestion on other markers but there would be multiple options https://pmc.ncbi.nlm.nih.gov/articles/PMC7744314/#:~:text=Moreover%2C%20although%20the%20majority%20of,neurons%20following%20neonatal%20tissue%20damage.
