Decoding Cellular Mechanisms for Mechanosensory Discrimination

Buchholtz, Lars J. von; Ghitani, Nima; Lam, Ruby M.; Licholai, Julia A.; Chesler, Alexander T.; Ryba, Nicholas J. P.

doi:10.1016/j.neuron.2020.10.028

Cited by 63 publications

(76 citation statements)

References 55 publications

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“…In marked contrast, mouse non-peptidergic, small diameter neurons are far more numerous than H10 and H11 accounting for 40% or the sensory neurons in mouse DRGs ( 29 ) and divide into 4 highly stereotyped transcriptional groups (Figure 1-figure supplement 2). Two of these classes of mouse neurons (NP2 and NP3) trigger itch ( 7, 36 ), one (NP1, expressing Mrgprd ) responds to noxious mechanical stimulation ( 14 ). NP1 neurons may have a role in mechano-nociception ( 5 ) and have recently been associated with suppression of skin inflammation ( 37 ), which was hypothesized as relevant for human health.…”

Section: Resultsmentioning

confidence: 99%

“…Some of these, like the cooling and menthol sensing receptor ( Trpm8 ) appear to define functional classes of cells ( 13 ). By contrast, the sense of touch appears to use a complex distributed code involving several different types of cells ( 14 ) to achieve its remarkable discriminatory power. For the most part, the human somatosensory system expresses the same range of functional genes as rodents ( 15 ) and exhibits similar responses to many types of stimulus ( 6, 8, 10, 12, 16, 17 ).…”

Section: Introductionmentioning

confidence: 99%

“…By contrast, most types of small diameter, slow conducting c-fibers terminate as free nerve endings both in mice and humans ( 6 ). Single cell sequencing approaches have produced a transcriptomic classification for mouse somatosensory neurons that corresponds well with their anatomy and function ( 5, 14, 24, 25 ). Intriguingly, in mice members of the Mrgpr-family of GPCRs mark at least two classes of small diameter neurons ( 24, 25 ).…”

Section: Introductionmentioning

confidence: 99%

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Single nucleus transcriptomic analysis of human dorsal root ganglion neurons

Nguyen

Buchholtz

Reker

et al. 2021

Preprint

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Somatosensory neurons with cell bodies in the dorsal root ganglia (DRG) project to the skin, muscles, bones, and viscera to detect touch and temperature as well as to mediate proprioception and many types of interoception. In addition, the somatosensory system conveys the clinically relevant noxious sensations of pain and itch. Here we used single nuclear transcriptomics to characterize the classes of human DRG neurons that detect these diverse types of stimuli. Notably, multiple types of human DRG neurons have transcriptomic features that resemble their mouse counterparts although expression of genes considered important for sensory function often differed between species. More unexpectedly, we demonstrated that several classes of mouse neurons have no direct equivalents in humans and human specific cell-types were also identified. This dataset should serve as a valuable resource for the community, for example as means of focusing translational efforts on molecules with conserved expression across species.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Single nucleus transcriptomic analysis of human dorsal root ganglion neurons

Nguyen

Buchholtz

Reker

et al. 2021

Preprint

Self Cite

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“…Delayed or immature transcriptional trajectories in gonadectomized mice (P50 at the time of harvest) ( Figure 3 ) suggests that aging is not the sole determinant of pubertal transcriptional alterations, but that circulating hormones are critical in this process. To cross-validate our trajectory analysis from the scRNAseq data as well as to examine its hormonal regulation, we performed highly multiplexed hybridization chain reaction FISH (HM-HCR FISH, V3), which we used to detect transcripts of ∼12 genes in 41,549 cells at single molecule resolution in situ ( Figure 4A-C and S4 ) (Choi et al, 2018; von Buchholtz et al, 2021) since the transcriptional states were determined by the combination of gene expressions. Besides the experimental groups used in scRNAseq experiments, we also prepared intact P28 male and female mice and hormonally supplemented groups receiving testosterone (male) or estrogen (female) from P23-P27 and harvested tissue at P28 to examine whether pubertal transcriptional trajectories were facilitated by early supplementation of circulating steroids.…”

Section: Resultsmentioning

confidence: 99%

“…Coronal sections were cut at 20 µm on a cryostat (Leica) and stored at -80°C until use. Sequential HCR fluorescent in situ hybridization (FISH) protocol was modified from the method described (von Buchholtz et al, 2021). Tissue sample was fixed with pre-chilled 4% paraformaldehyde (PFA) for 30 min on ice, followed by quick rinse in 1x PBS twice at room temperature (RT).…”

Section: Highly Multiplexed Hcr Fishmentioning

confidence: 99%

Pubertal sex hormones control transcriptional trajectories in the medial preoptic area

Hashikawa

Liu

et al. 2021

Preprint

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Pubertal maturation aids development of emotion, cognition, and reproduction. We investigated transcriptional dynamics in the medial preoptic area (MPOA), a hypothalamic center for reproductive behaviors, in male and female mice at single-cell resolution (scRNAseq) during puberty. Defined subsets of neurons expressing Slc32a1 and Esr1 (Vgat+ Esr1+) were the most transcriptionally dynamic compared to other cell types throughout puberty. These cell type specific transcriptional progressions towards adulthood were bidirectionally controlled by the levels of circulating testosterone and estradiol. Selective deletion of Esr1 in Slc32a1-expressing cells in the MPOA prior to puberty arrested transcriptional progression and revealed a sexually dimorphic gene-regulatory network governed by Esr1. Deletion of Esr1 in Vgat+ cells prevented the development of mating behavior in both sexes. These analyses reveal both sexually common and dimorphic transcriptional progressions during puberty as well as their regulatory mechanisms, which have important implications towards understanding adaptative and maladaptive processes governing adolescent brain development.

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Trigeminal neurons control immune-bone cell interaction and metabolism in apical periodontitis

Austah

Lillis

Akopian

et al. 2022

Cell. Mol. Life Sci.

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Apical periodontitis (AP) is an inflammatory disease occurring following tooth infection with distinct osteolytic activity. Despite increasing evidence that sensory neurons participate in regulation of non-neuronal cells, their role in the development of AP is largely unknown. We hypothesized that trigeminal ganglia (TG) Nav1.8+ nociceptors regulate bone metabolism changes in response to AP. A selective ablation of nociceptive neurons in Nav1.8Cre/Diphtheria toxin A (DTA)Lox mouse line was used to evaluate the development and progression of AP using murine model of infection-induced AP. Ablation of Nav1.8+ nociceptors had earlier progression of AP with larger osteolytic lesions. Immunohistochemical and RNAscope analyses demonstrated greater number of macrophages, T-cells, osteoclast and osteoblast precursors and an increased RANKL:OPG ratio at earlier time points among Nav1.8Cre/ DTALox mice. There was an increased expression of IL-1α and IL-6 within lesions of nociceptor-ablated mice. Further, co-culture experiments demonstrated that TG neurons promoted osteoblast mineralization and inhibited osteoclastic function. The findings suggest that TG Nav1.8+ neurons contribute to modulation of the AP development by delaying the influx of immune cells, promoting osteoblastic differentiation, and decreasing osteoclastic activities. This newly uncovered mechanism could become a therapeutic strategy for the treatment of AP and minimize the persistence of osteolytic lesions in refractory cases. Graphical abstract

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Decoding Cellular Mechanisms for Mechanosensory Discrimination

Cited by 63 publications

References 55 publications

Single nucleus transcriptomic analysis of human dorsal root ganglion neurons

Single nucleus transcriptomic analysis of human dorsal root ganglion neurons

Pubertal sex hormones control transcriptional trajectories in the medial preoptic area

Trigeminal neurons control immune-bone cell interaction and metabolism in apical periodontitis

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