A key role of PIEZO2 mechanosensitive ion channel in adipose sensory innervation [scRNA-seq]
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ABSTRACT:
PROVIDER: PRJNA1209114 | ENA |
REPOSITORIES: ENA
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Project description:Compared to the well-established functions of sympathetic innervation, the role of sensory afferents in adipose tissues remains less understood. Recent work revealed the anatomical and physiological significance of adipose sensory innervation; however, its molecular underpinning remains unclear. Here, using organ-targeted single-cell RNA sequencing, we identified the mechanoreceptor PIEZO2 as one of the most prevalent receptors in fat-innervating dorsal root ganglia (DRG) neurons. Selective PIEZO2 deletion in fat-innervating neurons led to molecular alternations in adipose tissue similar to DRG ablation. Conversely, a gain-of-function PIEZO2 mutant shifted the adipose phenotypes in the opposite direction. These results indicate that PIEZO2 plays a major role in the sensory regulation of adipose tissues. This discovery opens new avenues for exploring mechanosensation in organs not traditionally considered mechanically active, such as the adipose tissues, and therefore sheds light on the broader significance of mechanosensation in regulating organ function and homeostasis.
2025-02-02 | GSE286425 | GEO
Project description:Compared to the well-established functions of sympathetic innervation, the role of sensory afferents in adipose tissues remains less understood. Recent work revealed the anatomical and physiological significance of adipose sensory innervation; however, its molecular underpinning remains unclear. Here, using organ-targeted single-cell RNA sequencing, we identified the mechanoreceptor PIEZO2 as one of the most prevalent receptors in fat-innervating dorsal root ganglia (DRG) neurons. Selective PIEZO2 deletion in fat-innervating neurons led to molecular alternations in adipose tissue similar to DRG ablation. Conversely, a gain-of-function PIEZO2 mutant shifted the adipose phenotypes in the opposite direction. These results indicate that PIEZO2 plays a major role in the sensory regulation of adipose tissues. This discovery opens new avenues for exploring mechanosensation in organs not traditionally considered mechanically active, such as the adipose tissues, and therefore sheds light on the broader significance of mechanosensation in regulating organ function and homeostasis.
2025-02-02 | GSE286424 | GEO
Project description:A key role of PIEZO2 mechanosensitive ion channel in adipose sensory innervation [bulk RNA-seq]
| PRJNA1209116 | ENA
Project description:Tissue stiffening is a physical hallmark of solid tumor. In our study, we found that the mechanosensitive ion channel PIEZO1 can be tumor cells force sensor and transducer that regulate the altered tissue mechanics. We examined the transcriptional changes modulated by depletion of PIEZO1 in two human GBM cell lines. We found that with PIEZO1 KD, the components involved in ECM organization, focal adhesion formation, cytoskeleton, and mitosis, which contribute to tissue stiffness, are down-regulated.
2018-10-18 | GSE113261 | GEO
Project description:Mechanosensitive ion channel regulates tissue stiffening to promote glioma aggression
| PRJNA450606 | ENA
Project description:AbstractPiezo2 mechanotransduction channel is a crucial mediator of sensory neurons for sensing and transducing touch, vibration, and proprioception. We here characterized Piezo2 expression and cell specificity in rat peripheral sensory pathway using a validated Piezo2 antibody. Immunohistochemistry using this antibody revealed Piezo2 expression in pan primary sensory neurons of dorsal root ganglia in naïve rats, which was actively transported along afferent axons to both central presynaptic terminals innervating the spinal dorsal horn (DH) and peripheral afferent terminals in the skin. Piezo2 immunoreactivity (IR) was also detected in the postsynaptic neurons of the DH and in the motor neurons of the ventral horn, but not in spinal glial fibrillary acidic protein-positive and Iba1-positive glia. Notably, Piezo2-IR was clearly identified in peripheral nonneuronal cells, including perineuronal glia, Schwann cells in the sciatic nerve and surrounding cutaneous afferent endings, as well as in skin epidermal Merkel cells and melanocytes. Immunoblots showed increased Piezo2 in dorsal root ganglia ipsilateral to plantar injection of complete Freund's adjuvant, and immunostaining revealed increased Piezo2-IR intensity in the DH ipsilateral to complete Freund's adjuvant injection. This elevation of DH Piezo2-IR was also evident in various neuropathic pain models and monosodium iodoacetate knee osteoarthritis pain model, compared with controls. We conclude that (1) the pan neuronal profile of Piezo2 expression suggests that Piezo2 may function extend beyond simply touch or proprioception mediated by large-sized low-threshold mechanosensitive primary sensory neurons; (2) Piezo2 may have functional roles involving sensory processing in the spinal cord, Schwann cells, and skin melanocytes; and (3) aberrant Piezo2 expression may contribute pain pathogenesis.
| S-EPMC8526381 | biostudies-literature
Project description:The brush of a feather and a pinprick are perceived as distinct sensations because they are detected by discrete cutaneous sensory neurons. Inflammation or nerve injury can disrupt this sensory coding and result in maladaptive pain states, including mechanical allodynia, the development of pain in response to innocuous touch. However, the molecular mechanisms underlying the alteration of mechanical sensitization are poorly understood. In mice and humans, loss of mechanically activated PIEZO2 channels results in the inability to sense discriminative touch. However, the role of Piezo2 in acute and sensitized mechanical pain is not well defined. Here, we showed that optogenetic activation of Piezo2-expressing sensory neurons induced nociception in mice. Mice lacking Piezo2 in caudal sensory neurons had impaired nocifensive responses to mechanical stimuli. Consistently, ex vivo recordings in skin-nerve preparations from these mice showed diminished Aδ-nociceptor and C-fiber firing in response to mechanical stimulation. Punctate and dynamic allodynia in response to capsaicin-induced inflammation and spared nerve injury was absent in Piezo2-deficient mice. These results indicate that Piezo2 mediates inflammation- and nerve injury-induced sensitized mechanical pain, and suggest that targeting PIEZO2 might be an effective strategy for treating mechanical allodynia.
| S-EPMC6709986 | biostudies-literature
Project description:The study aimed to uncover the molecular profile of mouse Vglut2-possitive enteric neurons (VGLUT2-ENs) by single-cell mRNA sequencing (scRNA-seq). Method: We performed scRNA-seq of VGLUT2-ENs from distal intestine extracted from 6-8 weeks mice. We removed the non-neuronal cells, performed Principal Component Analysis (PCA) on the gene expression level of 15 well accepted and curated myenteric neuron markers, and analyzed the expression of the mechanosensitive ion channels. Results: clustering analysis results from PCA on the 15 gene markers indicates a dominant cluster of VGLUT2-ENs; By comparing the expression levels of the mechanosensitive ion channels Piezo1 and Piezo2 in the non-VGLUT2- ENs and VGLUT2-ENs, we find significantly less expression level of piezo1 and piezo2 genes in the VGLUT2-EN population as compared with myenteric neurons negative for VGLUT2. Conclusion: Molecular profiling of VGLUT2-ENs through single-cell mRNA sequencing unveiled a unique expression profile, distinguishing them from typical interneurons. Additionally, VGLUT2-ENs displayed minimal expression of mechanosensitive ion channels (Piezo1 and Piezo2), setting them apart from mechanosensitive interneurons.
2023-12-17 | GSE250388 | GEO
Project description:Protein kinase A is a downstream effector of many inflammatory mediators that induce pain hypersensitivity by increasing the mechanosensitivity of nociceptive sensory afferent. Here we examine the molecular mechanism underlying protein kinase-Adependent modulation of the mechanically-activated ion channel PIEZO2, which confers mechanosensitivity to many nociceptors. Using phosphorylation site prediction algorithms, we identified multiple putative and highly conserved PKA phosphorylation sites located on intracellular intrinsically disordered regions of PIEZO2. Site-directed mutagenesis and patch-clamp recordings showed that substitution of one or multiple putative PKA sites within a single intracellular domains does not alter PKA-induced PIEZO2 sensitization, whereas mutation of a combination of nine putative sites located on four different intracellular regions completely abolishes PKA-dependent PIEZO2 modulation, suggesting that the effect requires multisite phosphorylation. By demonstrating that PIEZO1 is not modulated by PKA, our data also reveals a previously unrecognized functional difference between PIEZO1 and PIEZO2. Moreover, by demonstrating that PKA only modulates PIEZO2 currents evoked by focal mechanical indentation of the cell, but not currents evoked by pressure-induced membrane stretch, we provide evidence suggesting that PIEZO2 is a polymodal mechanosensor that engages different protein domains for detecting different types of mechanical stimuli.
2023-07-20 | PXD041372 | Pride
Project description:Piezo2 is a mechanosensitive ion channel that plays critical roles in sensing touch and pain, proprioception, and regulation of heart rate. Global knockout of Piezo2 leads to perinatal lethality in mice, and Piezo2 gain-of-function mutations are associated with distal arthrogryposis, a disease characterized by congenital joint contractures. Emerging evidence suggests that Piezo channels (Piezo1 and Piezo2) can be regulated by their local membrane environment and particularly by cholesterol and phosphoinositides. To characterize the local Piezo2 lipid environment and investigate key lipid-protein interactions, we carried out coarse-grained molecular dynamics simulations of Piezo2 embedded in a complex mammalian membrane containing >60 distinct lipid species. We show that Piezo2 alters its local membrane composition such that it becomes enriched with specific lipids, such as phosphoinositides, and forms specific, long-term interactions with a variety of lipids at functionally relevant sites.
| S-EPMC9532583 | biostudies-literature