Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.01.182196v1?rss=1 Authors: Nayler, S., Agarwal, D., Curion, F., Bowden, R., Becker, E. Abstract: Current protocols for producing cerebellar neurons from human pluripotent stem cells (hPSCs) are reliant on animal co-culture and mostly exist as monolayers, which have limited capability to recapitulate the complex arrangement of the brain. We developed a method to differentiate hPSCs into cerebellar organoids that display hallmarks of in vivo cerebellar development. Single- cell profiling followed by comparison to an atlas of the developing murine cerebellum revealed transcriptionally-discrete populations encompassing all major cerebellar cell types. Matrigel encapsulated organoids displayed altered growth dynamics and differential regulation of cell cycle, migration and cell-death pathways. Encapsulated organoids also exhibited a greater degree of compositional variability. Furthermore, we showed the contribution of basement membrane signalling to both cellular composition of the organoids and developmentally-relevant gene expression programmes. This model system has exciting implications for studying cerebellar development and disease most notably by providing xeno-free conditions, representing a more biologically relevant and therapeutically tractable culture setting. Copy rights belong to original authors. Visit the link for more info