Generation of Human and Equine cerebral organoids from iPSCs: tools to study neurotropic viruses
Abstract
The brain is a complex organ and any model for studying it in its normal and pathological aspects becomes a tool of choice for neuroscientists. The mastering and dissemination of protocols allowing brain organoids development have paved the way for a whole range of new studies in the field of brain development, modeling of neurodegenerative or neurodevelopmental diseases, understanding tumors as well as infectious diseases that affect the brain. While studies are so far limited to the use of human cerebral organoids (hOCs), there is a growing interest in having similar models in other species. First, by applying differentiation protocol to human induced pluripotent cells (hiPSc), we generate hOCs expressing early and late markers depending on differentiation time. Then, we success to induced them in ventral or dorsal forebrain revealed by two distinct specific gene expressions. The dorsal hOCs were successfully infected by neurotropic henipavirus and permits to highlight antiviral effect of molecules in brain model. Second, by applying somatic reprogramming protocol to equine primary cells, we generate equine induced pluripotent stem cells (eq-iPSc). These cells exhibit stem cell-like characteristics and show a plasticity to be induced in different embryonic lineages including ectoderm, precursor of neural tissue. The application of dorsal hOCs protocol on eq-iPSc allows the expression of (early and late) neural markers in equine embryoid bodies suggesting the generation of equine cerebral organoid (eq-OCs). These OCs represent an important experimental tool to study species-specific neurotropic viruses, screen antiviral molecules and also to perform inter-species comparation of zoonotic viruses in brain model.
Domains
Life Sciences [q-bio]Origin | Files produced by the author(s) |
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