Piezo1 channels restrain ILC2s and regulate the development of airway hyperactivity [yoda1]
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ABSTRACT:
PROVIDER: PRJNA1076907 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27983868_1.fastq.gz | Fastqsanger.gz | |||
| SRR27983868_2.fastq.gz | Fastqsanger.gz | |||
| SRR27983869_1.fastq.gz | Fastqsanger.gz | |||
| SRR27983869_2.fastq.gz | Fastqsanger.gz | |||
| SRR27983870_1.fastq.gz | Fastqsanger.gz |
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Project description:Mechanosensitive ion channels sense force and pressure in immune cells to drive the inflammatory response in highly mechanical organs. Here we report that Piezo1 channels repress group 2 innate lymphoid cells (ILC2s)-driven type 2 inflammation in the lungs. Piezo1 is induced on lung ILC2s upon activation, as genetic ablation of Piezo1 in ILC2s increases their function and exacerbates the development of airway hyperreactivity (AHR). Conversely, Piezo1 agonist Yoda1 reduces ILC2-driven lung inflammation. Mechanistically, Yoda1 inhibits ILC2 cytokine secretion and proliferation in a KLF2-dependent manner, as we further found that Piezo1 engagement reduces ILC2 oxidative metabolism. Consequently, in vivo Yoda1 treatment notably reduces the development of AHR in experimental models of ILC2-driven allergic asthma. Human circulating ILC2s express and induce Piezo1 upon activation, as Yoda1 treatment of humanized mice reduces human ILC2-driven AHR. Our studies define Piezo1 as a critical regulator of ILC2s and we propose the potential of Piezo1 activation as a novel therapeutic approach for the treatment of ILC2-driven allergic asthma.
2024-02-20 | GSE255882 | GEO
Project description:Mechanosensitive ion channels sense force and pressure in immune cells to drive the inflammatory response in highly mechanical organs. Here we report that Piezo1 channels repress group 2 innate lymphoid cells (ILC2s)-driven type 2 inflammation in the lungs. Piezo1 is induced on lung ILC2s upon activation, as genetic ablation of Piezo1 in ILC2s increases their function and exacerbates the development of airway hyperreactivity (AHR). Conversely, Piezo1 agonist Yoda1 reduces ILC2-driven lung inflammation. Mechanistically, Yoda1 inhibits ILC2 cytokine secretion and proliferation in a KLF2-dependent manner, as we further found that Piezo1 engagement reduces ILC2 oxidative metabolism. Consequently, in vivo Yoda1 treatment notably reduces the development of AHR in experimental models of ILC2-driven allergic asthma. Human circulating ILC2s express and induce Piezo1 upon activation, as Yoda1 treatment of humanized mice reduces human ILC2-driven AHR. Our studies define Piezo1 as a critical regulator of ILC2s and we propose the potential of Piezo1 activation as a novel therapeutic approach for the treatment of ILC2-driven allergic asthma.
2024-02-20 | GSE255881 | GEO
Project description:Piezo1 channels restrain ILC2s and regulate the development of airway hyperactivity [piezo1KO]
| PRJNA1076906 | ENA
Project description:The mechanosensitive ion channels Transient Receptor Potential Vanilloid 4 (TRPV4) and PIEZO1 transduce physiologic and supraphysiologic magnitudes of mechanical signals in the chondrocyte, respectively. TRPV4 activation promotes chondrogenesis, while PIEZO1 activation by supraphysiologic deformations drives cell death. The mechanisms by which activation of these channels discretely drives changes in gene expression to alter cell behavior remains to be determined. To date, no studies have contrasted the transcriptomic response to activation of these channels, nor has any published data attempted to correlate these transcriptomes to alterations in cellular function. This study used RNA sequencing to comprehensively investigate the transcriptomes associated with activation of TRPV4 or PIEZO1, revealing that TRPV4 and PIEZO drive distinct transcriptomes, but also exhibit unique co-regulated clusters of genes. Notably, activation of PIEZO1 through supraphysiologic deformation induced a transient inflammatory profile that overlapped with the interleukin (IL)-1-responsive transcriptome and contained genes associated with cartilage degradation and osteoarthritis progression. However, both TRPV4 and PIEZO1 were also shown to elicit anabolic effects. PIEZO1 expression promoted a pro-chondrogenic transcriptome under unloaded conditions, and daily treatment with PIEZO1 agonist Yoda1 significantly increased sulfated glycosaminoglycan deposition in vitro. These findings emphasize the presence of a broad “mechanome” with distinct effects of TRPV4 and PIEZO1 activation in chondrocytes, suggesting complex roles for PIEZO1 in both the physiologic and pathologic responses of chondrocytes. The identification of transcriptomic profiles unique to or shared by PIEZO1 and TRPV4 (distinct from IL-1-induced inflammation) could inform future therapeutic designs targeting these channels for the management and treatment of osteoarthritis.
2024-06-05 | GSE269159 | GEO
Project description:Chondrocytes can potentially perceive mechanical stimuli via Piezo channels. We investigated the effect of the Piezo1 agonist Yoda1 on chondrocyte-like ATDC5 cells. Chondrocytes can potentially perceive mechanical stimuli via Piezo channels. We investigated the effect of the Piezo1 agonist Yoda1 on chondrocyte-like ATDC5 cells. Chondrocytes can potentially perceive mechanical stimuli via Piezo channels. We investigated the effect of the Piezo1 agonist Yoda1 on chondrocyte-like ATDC5 cells. Chondrocytes can potentially perceive mechanical stimuli via Piezo channels. We investigated the effect of the Piezo1 agonist Yoda1 on chondrocyte-like ATDC5 cells. We used microarray analysis to detail the global gene expression of ATDC5 cells in response to 6 hours of treatment with 5µM Yoda1.
2024-02-28 | GSE230071 | GEO
Project description:Group-2 innate-lymphoid cells (ILC2s) are critical mediators of the type-2 immune responses in multiple lung pathologies. We show that Piezo1, a mechanosensitive ion channel, plays a key role in regulating ILC2 functions by linking mechanical cues to biochemical signaling pathways. Both murine and human ILC2s strongly express Piezo1, and its activation by Yoda1 selectively enhances IL-13 production through calcium influx, which activates the mTOR-S6K pathway. This pathway leads to translational reprogramming, favoring IL-13 translation. Piezo1-deficient in ILC2s impairs this process, reducing IL-13 levels and resulting in attenuated lung inflammation and fibrosis in mouse models of IL-33- or Alternaria alternata-induced airway inflammation and bleomycin-induced fibrosis. These findings position Piezo1 as a critical mediator of ILC2-driven type-2 immune responses and highlight its potential as a therapeutic target for lung diseases characterized by excessive inflammation. This streamlined understanding of Piezo1 function improves focus on its mechanistic role in lung pathology.
2024-09-30 | GSE278085 | GEO
Project description:Group-2 innate-lymphoid cells (ILC2s) are critical mediators of the type-2 immune responses in multiple lung pathologies. We show that Piezo1, a mechanosensitive ion channel, plays a key role in regulating ILC2 functions by linking mechanical cues to biochemical signaling pathways. Both murine and human ILC2s strongly express Piezo1, and its activation by Yoda1 selectively enhances IL-13 production through calcium influx, which activates the mTOR-S6K pathway. This pathway leads to translational reprogramming, favoring IL-13 translation. Piezo1-deficient in ILC2s impairs this process, reducing IL-13 levels and resulting in attenuated lung inflammation and fibrosis in mouse models of IL-33- or Alternaria alternata-induced airway inflammation and bleomycin-induced fibrosis. These findings position Piezo1 as a critical mediator of ILC2-driven type-2 immune responses and highlight its potential as a therapeutic target for lung diseases characterized by excessive inflammation. This streamlined understanding of Piezo1 function improves focus on its mechanistic role in lung pathology.
2025-07-15 | GSE279338 | GEO
Project description:In gastric cancer (GC), PIEZO1 was suggested to promote cell migration by interacting with Trefoil factor family 1 (TFF1) and serve as a therapeutic target against invasion and metastasis. In addition, PIEZO1 demonstrates abundant expression in most GC cell lines and primary samples and highly-expressed PIEZO1 is associated with poor disease-specific survival. As Yoda1 is known to be an agonist of PIEZO1, we try to explore the PIEZO1 function in GC by Yoda1 treatment.
2023-12-08 | GSE228691 | GEO
Project description:The mechanosensitive ion channel PIEZO1 has emerged as a key regulator of vascular and skeletal biology. Here, we show that systemic activation of PIEZO1 using the chemical agonist Yoda1 in 3-week-old mice disrupts bone homeostasis by impairing type H endothelial cells and inhibiting osteogenic differentiation. In vivo, Yoda1 treatment significantly reduced the abundance of CD31hiEMCNhi type H vessels and altered trabecular bone microarchitecture without affecting total bone mass. In vitro, Yoda1 inhibited osteogenic gene expression and alkaline phosphatase activity in MC3T3-E1 preosteoblasts. Transcriptomic analysis of Yoda1-treated human bone microvascular endothelial cells (hBMECs) revealed a shift from an angiogenic H-type to a quiescent L-type, accompanied by upregulation of BMP signaling antagonists, particularly GREM1. Functional assays confirmed that GREM1 secreted from Yoda1-stimulated endothelial cells suppresses BMP4-induced osteoblast differentiation via paracrine signaling. Together, these findings uncover a novel endothelial-to-osteoblast regulatory axis mediated by PIEZO1-GREM1-BMP4 signaling, and underscore the context-dependent effects of PIEZO1 activation on bone regeneration.
2026-06-26 | GSE300884 | GEO
Project description:The mechanosensitive ion channel PIEZO1 has emerged as a key regulator of vascular and skeletal biology. Here, we show that systemic activation of PIEZO1 using the chemical agonist Yoda1 in 3-week-old mice disrupts bone homeostasis by impairing type H endothelial cells and inhibiting osteogenic differentiation. In vivo, Yoda1 treatment significantly reduced the abundance of CD31hiEMCNhi type H vessels and altered trabecular bone microarchitecture without affecting total bone mass. In vitro, Yoda1 inhibited osteogenic gene expression and alkaline phosphatase activity in MC3T3-E1 preosteoblasts. Transcriptomic analysis of Yoda1-treated human bone microvascular endothelial cells (hBMECs) revealed a shift from an angiogenic H-type to a quiescent L-type, accompanied by upregulation of BMP signaling antagonists, particularly GREM1. Functional assays confirmed that GREM1 secreted from Yoda1-stimulated endothelial cells suppresses BMP4-induced osteoblast differentiation via paracrine signaling. Together, these findings uncover a novel endothelial-to-osteoblast regulatory axis mediated by PIEZO1-GREM1-BMP4 signaling, and underscore the context-dependent effects of PIEZO1 activation on bone regeneration.
2026-06-26 | GSE300883 | GEO