Activation of Piezo1 induces heterogeneity in LSK cells leading to HSC proliferation and myelopoiesis [scRNA-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE285920 | GEO | 2025/11/03
REPOSITORIES: GEO
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Project description:We found that haematopoietic cell-specific Piezo1 knockout (KO) inhibits HSC proliferation and myeloid differentiation. To identify the underlying mechanism, we analysed the gene expression profiles of long-term haematopoietic stem cells (LT-HSCs) from Piezo1 KO mice and compared them with those from control mice. Our study demonstrated that the tight junction pathway was one of the enriched terms among downregulated genes in Piezo1 KO HSCs, with a decrease in JAM3 expression.
2025-11-03 | GSE285919 | 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: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: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:Although cells of the immune system experience force and pressure throughout their lifecycle, almost nothing is known about how these mechanical processes regulate the immune response. Immune cells in highly mechanical organs, such as the lung, are constantly exposed to tonic and dynamically changing mechanical cues. Here using reverse genetics, we show that myeloid cells respond to force and alterations in cyclical hydrostatic pressure (CHP) via the mechanosensory ion channel (MSIC) PIEZO1. Unbiased RNA-sequencing from macrophages subjected to CHP reveals a striking state of proinflammatory reprogramming. We report a novel mechanosensory-immune signaling circuit which PIEZO1 initiates in response to CHP, activating c-JUN, upregulating Endothelin-1 (EDN1), and stabilizing HIF1α to facilitate a prolonged program of proinflammatory mediators. Using mice conditionally deficient of PIEZO1 in myeloid cells, and cellular depletion assays, we show infiltrating monocytes respond to cyclical force to recruit neutrophils and clear pulmonary Pseudomonas aeruginosa infection. Furthermore, myeloid PIEZO1 also drove lung pathology in a mouse model of pulmonary fibrosis. Our results demonstrate a novel environmental sensory axis that myeloid cells recognize to mount an inflammatory response, and is the first report showing a physiological role for PIEZO1 and mechanosensation in immunity.
2019-08-21 | GSE133069 | GEO
Project description:Angiopoietin-Tie1 signaling is required for lymphatic vascular integrity and both ANGPT2 and TIE1 genetic variants have been associated with lymphedema in patients1, 2. Concurrent with growth-factor signaling, mechanical forces sensed by lymphatic endothelial cells (LECs) are also needed to regulate lymphatics3, 4. How these two pathways might interact in the lymphatic system is unknown. Here, we identified a regulatory network in LECs linking activation of the mechanosensory channel, PIEZO1 to Angiopoietin-Tie signaling and repression of a downstream FOXO1 transcriptional response. RNAseq analysis of dermal LECs from Tie1-deficient embryos showed persistent FOXO1 activity with downregulation of LEC-associated genes including Ccl21a, Foxc2, Gata2 and Gja4, as well as increased expression of the mechanosensory channel, Piezo1. Activation of PIEZO1 in human dermal LECs (HDLECs) by the small molecule agonist, Yoda1, triggered exocytosis of the Tie ligand, Angiopoietin-2 (ANGPT2), activation of Tie/AKT/PI3K signaling and export of FOXO1 out of the nucleus. Our data identify a novel molecular pathway linking mechano-transduction to ANGPT2-Tie1 activity and dynamic modulation of FOXO1 activity needed for patterning and function of the lymphatic system
2024-03-05 | GSE211849 | GEO
Project description:Glucocorticoid-induced osteoporosis (GIOP) lacks fully effective treatments. This study investigated the role of Piezo1, a mechanosensitive ion channel component 1, in GIOP. We found reduced Piezo1 expression in cortical bone osteocytes from patients with GIOP and a GIOP mouse model. Yoda1, a Piezo1 agonist, enhanced the mechanical stress response and bone mass and strength, which were diminished by dexamethasone (DEX) administration in GIOP mice. RNA sequencing revealed that Yoda1 elevated Piezo1 expression by activating the key transcription factor Hes1, followed by enhanced CaM kinase II and Akt phosphorylation in osteocytes. This improved lacuno-canalicular network and reduced sclerostin production and receptor activator of nuclear factor kappa beta/osteoprotegerin ratio, which were mitigated by DEX. Comparative analysis of mouse models and human GIOP cortical bone revealed downregulation of mechano-stimulated osteogenic factors, such as osteocrin, and cartilage differentiation markers in osteoprogenitor cells. In human periosteal-derived cells, DEX suppressed differentiation into osteoblasts, but Yoda1 rescued this effect. Our findings suggest that reduced Piezo1 expression and activity in osteocytes and periosteal cells contribute to GIOP, and Yoda1 may offer a novel therapeutic approach by restoring mechanosensitivity.
2024-12-18 | GSE276391 | GEO
Project description:Glucocorticoid-induced osteoporosis (GIOP) lacks fully effective treatments. This study investigated the role of Piezo1, a mechanosensitive ion channel component 1, in GIOP. We found reduced Piezo1 expression in cortical bone osteocytes from patients with GIOP and a GIOP mouse model. Yoda1, a Piezo1 agonist, enhanced the mechanical stress response and bone mass and strength, which were diminished by dexamethasone (DEX) administration in GIOP mice. RNA sequencing revealed that Yoda1 elevated Piezo1 expression by activating the key transcription factor Hes1, followed by enhanced CaM kinase II and Akt phosphorylation in osteocytes. This improved lacuno-canalicular network and reduced sclerostin production and receptor activator of nuclear factor kappa beta/osteoprotegerin ratio, which were mitigated by DEX. Comparative analysis of mouse models and human GIOP cortical bone revealed downregulation of mechano-stimulated osteogenic factors, such as osteocrin, and cartilage differentiation markers in osteoprogenitor cells. In human periosteal-derived cells, DEX suppressed differentiation into osteoblasts, but Yoda1 rescued this effect. Our findings suggest that reduced Piezo1 expression and activity in osteocytes and periosteal cells contribute to GIOP, and Yoda1 may offer a novel therapeutic approach by restoring mechanosensitivity.
2024-12-18 | GSE276529 | GEO
Project description:PIEZO1 is a mechanically-activated ion channel that contributes to flow sensing in vascular endothelium. Moreover, deletion of endothelial PIEZO1 was recently found to suppress activation of Notch1 target genes in hepatic microvascular endothelium. Here, because of the liver’s dominant role in lipid regulation, we set out to test the novel hypothesis that endothelial PIEZO1 regulates hepatic lipid homeostasis. We performed bulk RNA sequencing on PIEZO1-deleted mice exposed to chow and high fat diets. Our transcriptomics analysis reveal unexpected relevance to lipid and glucose homeostasis.
2024-06-29 | E-MTAB-9996 | biostudies-arrayexpress
Project description:Tyrosine kinase inhibitors (TKIs) have improved cancer outcomes but are limited by cardiovascular toxicity, most notably hypertension and heart failure. The underlying mechanisms remain poorly understood, hindering the development of protective strategies. Here, we investigated the role of endothelial mechanotransduction in mediating vascular and cardiac injury caused by the VEGFR-targeting TKI sunitinib. Using patient-specific induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) and a mouse model of TKI-induced hypertension, we identified downregulation of PIEZO1, a mechanically activated ion channel, as a central driver of endothelial dysfunction. Restoring PIEZO1 expression, either pharmacologically with Yoda1, a selective agonist, or through inducible overexpression in iPSC-ECs, reversed sunitinib-induced endothelial dysfunction and mitigated its hypertensive effects, providing both mechanistic and genetic validation of PIEZO1’s protective role against vascular toxicity. In mice, Yoda1 co-treatment prevented the long-term cardiac dysfunction observed following sunitinib exposure, and normalized elevations in circulating cardiac stress biomarkers. Single-nuclei multiomic profiling of mouse hearts revealed that sunitinib exposure activated chromatin remodeling and fibrogenic programs, which were reversed with PIEZO1 activation. Human engineered cardiac organoids further demonstrated that sunitinib impaired cardiomyocyte function only in the presence of endothelial cells, confirming a role for disrupted endothelial-cardiomyocyte crosstalk in TKI cardiotoxicity. Together, these findings identify endothelial PIEZO1 as a critical mediator of TKI-induced hypertension and cardiac dysfunction and highlight PIEZO1 activation as a potential therapeutic strategy for protecting cardiovascular health during cancer therapy.
2025-11-10 | GSE309753 | GEO