Gene expression profile at single cell level of skin cells from back skin of control and Piezo1 inducible knock-out mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE266896 | GEO | 2025/04/04
REPOSITORIES: GEO
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Project description:Piezo1 is a mechanosensitive ion channel that has gained recognition for its role in regulating diverse physiological processes. However, the influence of Piezo1 in inflammatory disease, including infection and tumor-immunity, is not well-studied. We postulated that Piezo1 links physical forces to immune regulation in myeloid cells. We discovered signal transduction via Piezo1 in myeloid cells and established this channel as the primary sensor of mechanical stress in these cells. Global inhibition of Piezo1 was protective against both cancer and septic shock and resulted in a diminution in suppressive myeloid cells. Moreover, deletion of Piezo1 in myeloid cells protected against cancer and increased survival in poly-microbial sepsis. Mechanistically, we show that mechanical stimulation promotes Piezo1-dependent myeloid cell expansion by suppressing Rb. We further show Piezo1-mediated silencing of Rb is regulated via upregulation of HDAC2. Collectively, our work uncovers Piezo1 as a targetable immune checkpoint that drives immune-suppressive myelopoiesis in cancer and infectious disease.
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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.
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Project description:Foxi3 is a transcription factor expressed in the hair follicle epithelium during development and postnatally. In this study we used a microarray analysis to indentify differentially expressed genes in Foxi3 null epithelium compared to Foxi3 wt epithelium. We used E15.5 stage as the earliest time point when the Foxi3 null hair phenotype bacame obvious, to find out the most early consequences of Foxi3 ablation. Dispase-dissociated back skin epithelia of 4 Foxi3 total null and 4 wild-type E15.5 mouse embryos, littermates from 4 litters of C57/Bl6 background, were used for the analysis. Array and data analysis were performed in the Biomedicum Functional Genomics Unit (University of Helsinki, Finland).
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