Self-organizing Single-Rosette Brain Organoids from Human Pluripotent Stem Cells [article]

Andrew M Tidball, Wei Niu, Qianyi Ma, Taylor N Takla, J Clayton Walker, Joshua L Margolis, Sandra P Mojica-Perez, Roksolana Sudyk, Shannon J Moore, Ravi Chopra, Vikram G Shakkottai, Geoffrey G Murphy (+2 others)
2022 bioRxiv   pre-print
The field of brain organoid research is complicated by morphological variability with multiple neural rosette structures per organoid. We have developed a new human brain organoid technique that generates self-organizing, single-rosette spheroids (SOSRS) with reproducible size, cortical-like lamination, and cell diversity. Rather than patterning a 3-dimensional embryoid body, we initiate brain organoid formation from a 2-dimensional monolayer of human pluripotent stem cells (hPSCs) that is
more » ... rned with small molecules into neuroepithelium and differentiated to cells of the developing dorsal cerebral cortex. This approach recapitulates the 2D to 3D transition from neural plate to neural tube that occurs during neurodevelopment. The vast majority of monolayer fragments form spheres with a single central lumen and consistent growth rates. Over time, the SOSRS develop appropriately ordered lamination consistent with six cortical layers by immunocytochemistry and single cell RNA-sequencing. The reproducibility of this method has allowed us to demonstrate robust structural phenotypes arising from chemical teratogen exposure or when modeling a genetic neurodevelopmental epileptic disorder. This platform should advance studies of human cortical development, brain disorder mechanisms, and precision therapies.
doi:10.1101/2022.02.28.482350 fatcat:26dmxxgouzgbtp5yyy7ehzue3q