![]() ![]() However, there has been no method to study the hominid brain directly due to a lack of appropriate approaches. Model animals and genomic studies help us to analyze brain structure and evolution. ![]() These results suggest that controlling fluid dynamics by biomechanical engineering can direct stem cell differentiation of brain organoids, and that inverted brain organoids will be applicable for studying human brain development and disorders in the future.Ĭlarifying the principles regarding how brain cells arise and assemble tissue is important for understanding brain development and disease mechanisms. Single-cell RNA sequencing revealed that neurons of inverted brain organoids presented a GABAergic character of the ventral forebrain. ![]() Primary cilia of neural progenitors by vertical mixing were aligned in a multidirectional manner, and those by orbital mixing in a bidirectional manner. To uncover the mechanisms of the inverted structure, we investigated the direction of primary cilia, a cellular mechanosensor. Computational analysis of flow dynamics clarified that, by comparison with orbital mixing, vertical mixing maintained the high turbulent energy around organoids, and continuously kept inter-organoid distances by dispersing and adding uniform rheological force on organoids. The organoids generated by vertical mixing showed neurons that migrated from the outer periphery to the inner core of organoids, in contrast to orbital mixing. Here we examined the vertical-mixing effect on brain organoid structures using bioreactors and established inverted brain organoids. Organoid technology provides an opportunity to generate brain-like structures by recapitulating developmental steps in the manner of self-organization. ![]()
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