Project description:The human brain is highly sensitive to oxygen availability, and hypoxia is a common risk factor for neurological and cognitive traits throughout life. Hypoxia exerts distinct effects on different brain cell types, many of which involve changes in gene expression. We used brain organoids derived from genotyped human iPSC lines to characterize gene expression at single-cell resolutions under normoxic conditions and both hypoxic and hyperoxic challenges.
Project description:Dopamine signaling in the adult ventral forebrain regulates behavior, stress response, and memory formation and in neurodevelopment regulates neural differentiation and cell migration. Excessive dopamine levels including due to cocaine use both in utero and in adults could lead to long-term adverse consequences. The mechanisms underlying both homeostatic and pathological changes remain unclear, partly due to the diverse cellular responses elicited by dopamine and the reliance on animal models that exhibit species-specific differences in dopamine signaling. To address these limitations, 3-D cerebral organoids have emerged as human-derived models, recapitulating salient features of human cell signaling and neurodevelopment. Organoids have demonstrated responsiveness to external stimuli, including substances of abuse, making them valuable investigative models. In this study we utilize the Xiang-Tanaka ventral forebrain organoid model and characterize their response to acute and chronic dopamine or cocaine exposure. The findings revealed a robust immune response, novel response pathways, and a potential critical role for reactive oxygen species (ROS) in the developing ventral forebrain. These results highlight the potential of cerebral organoids as in vitro human models for studying complex biological processes in the brain.
Project description:Dopamine signaling in the adult ventral forebrain regulates behavior, stress response, and memory formation and in neurodevelopment regulates neural differentiation and cell migration. Excessive dopamine levels including due to cocaine use both in utero and in adults could lead to long-term adverse consequences. The mechanisms underlying both homeostatic and pathological changes remain unclear, partly due to the diverse cellular responses elicited by dopamine and the reliance on animal models that exhibit species-specific differences in dopamine signaling. To address these limitations, 3-D cerebral organoids have emerged as human-derived models, recapitulating salient features of human cell signaling and neurodevelopment. Organoids have demonstrated responsiveness to external stimuli, including substances of abuse, making them valuable investigative models. In this study we utilize the Xiang-Tanaka ventral forebrain organoid model and characterize their response to acute and chronic dopamine or cocaine exposure. The findings revealed a robust immune response, novel response pathways, and a potential critical role for reactive oxygen species (ROS) in the developing ventral forebrain. These results highlight the potential of cerebral organoids as in vitro human models for studying complex biological processes in the brain.
Project description:Organoids were generated from H9 cells. Single cells were sorted from 4-month-old brain organoids differentiated using the telencephalon organoids protocol.
Project description:We generated cortical organoids from four FCD patients. To generate cortical organoids, we used induced pluriplotent stem cells (iPSCs) obtained from skin biopsy from these FCD selected patients and healthy controls. We extrated RNA samples from the cortical organoids to do customized panel of gene expression. Gene expression using NanoString Human Neuropathology Panel from four FCD patients and four controls