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bioRxiv · 10.1101/2025.10.08.681038

Mechanical stretch disrupts calcium dynamics and redistributes Piezo1 in human astrocytes

Shiravi, S.·Chakka, A.·Xiao, X.·Garcia, M. F.·Yufa, A.·Mitevska, A.·Seah, C.·Huckins, L. M.·Brennand, K.·Finan, J. D.
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Abstract

Astrocytes regulate the activity of nearby neurons so disruption of astrocyte calcium dynamics by traumatic brain injury (TBI) could have profound consequences for neural network activity in the brain. In this study, human induced pluripotent stem cell (hiPSC)-derived astrocytes were used in a two-dimensional (2D) in vitro stretch injury model to evaluate the effect of trauma on calcium dynamics, mitochondrial function, and the mechanosensitive ion channel Piezo1. Outcomes were assessed using live imaging, immunostaining, and RNA sequencing. Cell viability, mitochondrial membrane potential, and spontaneous calcium transients declined as injury severity increased. At moderate injury severity, the decreases in mitochondrial membrane potential and calcium dynamics were temporary. The spatial distribution of Piezo1 also changed temporarily after injury. RNA sequencing identified 196 genes that changed expression after injury, including downregulation of mitochondrial and oxidative metabolic processes and upregulation of cortical thinning pathways. These findings establish this model as a platform for investigating the cellular mechanisms of TBI and its influence on neurodegeneration.

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Shiravi, S., Chakka, A., Xiao, X., Garcia, M. F., Yufa, A., Mitevska, A., Seah, C., Huckins, L. M., Brennand, K., Finan, J. D.. 2025-10-09. Mechanical stretch disrupts calcium dynamics and redistributes Piezo1 in human astrocytes. https://doi.org/10.1101/2025.10.08.681038

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