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RNA-seq of wildtype and PIEZO1 knockout mice livers to investigate lipid and glucose regulation by the endothelial force sensor PIEZO1

ABSTRACT: RNA-seq of wildtype and PIEZO1 knockout mice livers to investigate lipid and glucose regulation by the endothelial force sensor PIEZO1

PROVIDER: PRJEB42430 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR5083570_1.fastq.gz	Fastqsanger.gz
	ERR5083570_2.fastq.gz	Fastqsanger.gz
	ERR5083580_1.fastq.gz	Fastqsanger.gz
	ERR5083580_2.fastq.gz	Fastqsanger.gz
	ERR5083590_1.fastq.gz	Fastqsanger.gz

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RNA-seq of wildtype and PIEZO1 knockout mice livers to investigate lipid and glucose regulation by the endothelial force sensor PIEZO1

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

Reevaluation of Piezo1 as a gut RNA sensor

Project description:Piezo1 is a stretch-gated ion channel required for mechanosensation in many organ systems. Recent provocative findings describe a new role for Piezo1 in the gut, suggesting that it is a sensor of microbial single-stranded RNA (ssRNA) rather than mechanical force. If true, this would redefine the scope of Piezo biology. Here, we sought to replicate the central finding that fecal ssRNA is a natural agonist of Piezo1. While we observed that fecal extracts and ssRNA stimulate calcium influx in certain cell lines, this response was independent of Piezo1. Additionally, sterilized dietary extracts devoid of gut biome RNA showed similar cell line-specific stimulatory activity to fecal extracts. Together, our data highlight potential confounds inherent to gut-derived extracts, exclude Piezo1 as a receptor for ssRNA in the gut, and support a dedicated role for Piezo channels in mechanosensing.

2022-11-16 | GSE213903 | GEO

Piezo1 integration of vascular architecture with physiological force LC-MSMS

Project description:The mechanisms by which physical forces regulate cells to determine complexities of vascular structure and function are enigmatic. Here we show the role the ion channel subunit Piezo1 (FAM38A). Disruption of mouse Piezo1 gene disturbed vascular development and was embryonic lethal within days of the heart beating to cause blood flow. Importance of Piezo channels as sensors of blood flow was indicated by Piezo1 dependence of shear stress-evoked ionic current and calcium influx in endothelial cells and the ability of exogenous Piezo1 to confer shear stress sensitivity on cells that otherwise lacked. Downstream of this calcium influx was proteoase activity and spatial organization of endothelial cells to the polarity of the applied force. Without Piezo1, normal endothelial cell organization was lacking. The data suggest Piezo1 channels as pivotal integrators of vascular architacture with physiological mechanical force.

2014-08-08 | PXD001099 | Pride

Mechanical force coordinates with estrogen to orchestrate alveolar bone homeostasis via PIEZO1

Project description:Healthy alveolar bone is the cornerstone for oral function and oral treatment. In the aging population, increasingly postmenopausal women requiring dental services experiences alveolar bone loss due to estrogen deficiency. Both local factors (occlusal force lose) and systemic factors (estrogen deficiency) affects their alveolar bone health, but the association remains to be clarified. Here, we identified that occlusal force is critical in maintaining alveolar bone mass and PIEZO1 coordinates mechanical force and estrogen, thus orchestrating alveolar bone homeostasis. Mechanistically, both occlusal force loss and PIEZO1 deletion may impair the osteogenesis of alveolar bone and sequentially regulate catabolic metabolism through Fas ligand (FasL)-induced osteoclastic apoptosis. PIEZO1 may promote the activity of signal transducer and activator of transcription 3 (STAT3) and estrogen receptor 1 (ESR1), which cooperatively increase Fasl transcription. This study thus revealed a cooperation between occlusal force and estrogen in maintaining alveolar bone homeostasis through a PIEZO1-STAT3/ESR1-FasL pathway. Our work supports restoration of occlusal force with dental therapies early and suggests that preventing alveolar bone loss is the major priority. PIEZO1 may serve not only as a treatment target for occlusal force loss-induced alveolar bone loss but also as a potential target for metabolic bone loss, especially in older patients.

2025-12-31 | GSE205377 | GEO

Mechanosensation of Cyclical Force by PIEZO1 is Essential for Innate Immunity

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

Reevaluation of Piezo1 as a gut RNA sensor

Project description:Reevaluation of Piezo1 as a gut RNA sensor

| PRJNA882906 | ENA

Mechanosensation of Cyclical Force by PIEZO1 is Essential for Innate Immunity

Project description:Mechanosensation of Cyclical Force by PIEZO1 is Essential for Innate Immunity

| PRJNA549874 | ENA

Piezo1 mediated mechanotransduction modulates macrophages proliferation during bone remodeling via PI3K-AKT-Ccnd1 axis

Project description:Macrophages play a pivotal role in mechanical force-induced inflammatory bone remodeling. Yet, how macrophages perceive mechanical stimuli and thereby modulate biological behaviors remain elusive. The orthodontic tooth movement (OTM) model was established to access the role of Piezo1 in modulating macrophage response upon mechanical stimuli. The potential functions and molecule mechanisms of Piezo1 were explored by bone marrow-derived macrophages (BMDMs) using mechanical stretch system, western blotting, immunofluorescence, flow cytometry and RNA sequencing. We first found macrophage proliferative phenotype enhanced at the later stage of force application. The biological variation mediated by mechanical force could be suppressed by Piezo1 inhibition. Furthermore, Piezo1 activated PI3K-AKT signaling was closely associated with macrophage proliferation upon mechanical stimuli. Additionally, Ccnd1 was authenticated as a critical downstream factor of PI3K-AKT signaling and conditional ablation of Ccnd1 in macrophages inhibited macrophage proliferation in mechanical force-induced bone remodeling procedure.

2024-12-08 | GSE190470 | GEO

Mechanical force coordinates with estrogen to orchestrate alveolar bone homeostasis via PIEZO1

Project description:Mechanical force coordinates with estrogen to orchestrate alveolar bone homeostasis via PIEZO1

| PRJNA844902 | ENA

Role of Piezo1-mediated mechanotransduction in osteocyte differentiation

Project description:Mechanical force is a fundamental regulator of bone development and homeostasis. Mechanosensitive osteocytes are the most abundant bone cells that form interconnected dendrites to respond to mechanical stimuli and interact with the bone-forming osteoblasts and the bone-remodeling osteoclasts. However, the molecular mechanisms underlying osteocyte maturation and dendrite formation remain unclear. By generating a Piezo1 "knock-out" osteocyte cell line, we identified a key role of Piezo1-mediated mechanotransduction in osteocyte differentiation. QRT-PCR analysis revealed delayed osteocyte differentiation in the Piezo1 KO cells relative to WT cells. By performing bulk RNA sequencing of WT and Piezo1 KO OCY454 cells at early (D1), intermediate (D14), and late (D28) stages of differentiation allowed for the identification of key signaling pathways in driving normal osteocyte dfiferentiation, as well as those regulated by Piezo1 mechanotransduction.

2024-09-20 | GSE277264 | GEO

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