Human vs. Mouse Nociceptors – Similarities and Differences

Rostock, Charlotte; Schrenk-Siemens, Katrin; Pohle, Jörg; Siemens, Jan

doi:10.1016/j.neuroscience.2017.11.047

Cited by 131 publications

(134 citation statements)

References 69 publications

(118 reference statements)

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“…For example, NF200 is expressed in all sensory neurons in human DRG [39] and CGRP and IB4 significantly overlap in rat DRG [36]. Similarly, we identified a large population of CGRP and P2X3R co-expressing neurons in human DRG that was not present in mouse.…”

Section: Discussionsupporting

confidence: 54%

“…Approximately 29.9% and 31.7% of the neurons in mouse and human, respectively, were negative for CGRP and/or P2X3R mRNA expression. These neurons in mice were large diameter NF200-positive neurons ( Fig 1G); but because NF200 antibodies label all DRG neurons in humans [39], we were unable to label these cells with a clear neurochemical marker initially. However, further analyses of other mRNA targets in human revealed that these CGRP/P2X3R mRNA-negative neurons were large diameter cells, fitting the size profile for an A-β mechanoreceptor, and expressing some specific neurochemical markers (for example KCNS1).…”

Section: Calca (Cgrp) and P2rx3 (P2x3r) Label Distinct Neuronal Subpomentioning

confidence: 94%

“…Given the non-specificity for NF200 in human DRG [39], IHC for NF200 was only conducted on mouse tissues.…”

Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

“…However, long-standing evidence supports these markers may not exclusively demarcate DRG neuronal subpopulations in other species. For instance, studies in rats have shown that there is a large overlap in the expression of CGRP and IB4-positive neurons in DRG [36] and NF200 marks all sensory neurons in human DRG [39]. Relatively few previous studies have quantitatively investigated the expression and population distribution for a broad number of mRNA targets in both mouse and human DRG, although several studies have found important differences using bulk RNA-seq, physiological or histochemical measures [19].…”

Section: Introductionmentioning

confidence: 99%

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Quantitative differences in neuronal subpopulations between mouse and human dorsal root ganglia demonstrated with RNAscopein situhybridization

Shiers

Klein

Price

2020

Preprint

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Next generation transcriptomics in combination with imaging-based approaches have emerged as powerful tools for the characterization of dorsal root ganglion (DRG) neuronal subpopulations. The mouse DRG has been wellcharacterized by many independently conducted studies with convergent findings, but few studies have directly compared expression of population markers between mouse and human. This is important because of our increasing reliance on the mouse as a preclinical model for translational studies. While calcitonin gene-related peptide (CGRP) and P2X purinergic ion channel type 3 receptor (P2X3R) have been used to define peptidergic and non-peptidergic nociceptor subpopulations, respectively, in mouse DRG, these populations may be different in other species. To directly test this, as well as a host of other markers, we used multiplex RNAscope in-situ hybridization to elucidate the distribution of a multitude of unique and classic neuronal mRNAs in peptidergic (CGRP expressing) and non-peptidergic (P2X3R expressing) nociceptor subpopulations in mouse and human DRG. We found a large overlapping CGRP and P2X3R neuronal subpopulation in human, lumbar DRG that was not present in mouse. We also found differential expression in a variety of mRNAs for Trp-channels, cholinergic receptors, potassium channels, sodium channels, other markers/targets. These data offer insights into the spatial and functional organization of neuronal cell subpopulations in the rodent and human DRG and support the idea that sensory system organizational principles are likely different between both species.

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Section: Discussionsupporting

confidence: 54%

Section: Calca (Cgrp) and P2rx3 (P2x3r) Label Distinct Neuronal Subpomentioning

confidence: 94%

“…Given the non-specificity for NF200 in human DRG [39], IHC for NF200 was only conducted on mouse tissues.…”

Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Quantitative differences in neuronal subpopulations between mouse and human dorsal root ganglia demonstrated with RNAscopein situhybridization

Shiers

Klein

Price

2020

Preprint

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“…In native mouse and human DRGs, another TRP ion channel, TRPA1, is expressed in a subset of TRPV1-positive neurons (Rostock et al, 2018).…”

Section: Functional Characterization Of Trka-positive Neuronsmentioning

confidence: 99%

HESC-derived sensory neurons reveal an unexpected role for PIEZO2 in nociceptor mechanotransduction

Schrenk-Siemens

Pohle

Rostock

et al. 2019

Preprint

Self Cite

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Somatosensation, the detection and transduction of external and internal stimuli, has fascinated scientists for centuries. But still, some of the mechanisms how distinct stimuli are detected and transduced are not entirely understood. Over the past decade major progress has increased our understanding in areas such as mechanotransduction or sensory neuron classification. Additionally, the accessibility to human pluripotent stem cells and the possibility to generate and study human sensory neurons has enriched the somatosensory research field.Based on our previous work, the generation of functional human mechanoreceptors, we describe here the generation of hESC-derived nociceptor-like cells. We show that by varying the differentiation strategy, we can produce different nociceptive subpopulations. One protocol in particular allowed the generation of a sensory neuron population, homogeneously expressing TRPV1, a prototypical marker for nociceptors. Accordingly, we find the cells to homogenously respond to capsaicin, to become sensitized upon inflammatory stimuli, and to respond to temperature stimulation. Surprisingly, all of the generated subtypes show mechano-nociceptive characteristics and, quite unexpectedly, loss of mechanotransduction in the absence of PIEZO2.

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NOCICEPTRA: Gene and microRNA Signatures and Their Trajectories Characterizing Human iPSC‐Derived Nociceptor Maturation

et al. 2021

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Nociceptors are primary afferent neurons serving the reception of acute pain but also the transit into maladaptive pain disorders. Since native human nociceptors are hardly available for mechanistic functional research, and rodent models do not necessarily mirror human pathologies in all aspects, human induced pluripotent stem cell‐derived nociceptors (iDN) offer superior advantages as a human model system. Unbiased mRNA::microRNA co‐sequencing, immunofluorescence staining, and qPCR validations, reveal expression trajectories as well as miRNA target spaces throughout the transition of pluripotent cells into iDNs. mRNA and miRNA candidates emerge as regulatory hubs for neurite outgrowth, synapse development, and ion channel expression. The exploratory data analysis tool NOCICEPTRA is provided as a containerized platform to retrieve experimentally determined expression trajectories, and to query custom gene sets for pathway and disease enrichments. Querying NOCICEPTRA for marker genes of cortical neurogenesis reveals distinct similarities and differences for cortical and peripheral neurons. The platform provides a public domain neuroresource to exploit the entire data sets and explore miRNA and mRNA as hubs regulating human nociceptor differentiation and function.

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Human vs. Mouse Nociceptors – Similarities and Differences

Cited by 131 publications

References 69 publications

Quantitative differences in neuronal subpopulations between mouse and human dorsal root ganglia demonstrated with RNAscopein situhybridization

Quantitative differences in neuronal subpopulations between mouse and human dorsal root ganglia demonstrated with RNAscopein situhybridization

HESC-derived sensory neurons reveal an unexpected role for PIEZO2 in nociceptor mechanotransduction

NOCICEPTRA: Gene and microRNA Signatures and Their Trajectories Characterizing Human iPSC‐Derived Nociceptor Maturation

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