Effects of minocycline and rapamycin in gamma-irradiated human embryonic stem cells-derived cerebral organoids
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Radiation induces DNA and protein damage and free radical formation, effectively establishing cellular senescence in a variety of models. We demonstrate the effects of two known pleiotropic drugs following gamma radiation damage in neurosphere/cerebral organoid system based on human embryonic stem cells. mTORC1 repression by rapamycin prior to irradiation, or metabolic activation by minocycline after irradiation, partially rescues neuroepithelium integrity, neurite-growing capacity, ventricle formation and extracellular acidification rate as an integral measure of metabolic output. Cerebral organoid model thus provides valid and robust readouts for radiation studies in a complex 3D setting.
KeywordsRadiation Neural development Pluripotent stem cells Cerebral organoids Minocycline Rapamycin
The authors are grateful to Prof. Yu-Chieh Wang and Victor Lin (UNTHSC) for their training and inspiration in hESCs and organoid work.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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