Effects of early geometric confinement on the transcriptomic profile of human cerebral organoids

摘要: BackgroundBiophysical factors such as shape and mechanical forces are known to play crucial roles in stem cell differentiation, embryogenesis neurodevelopment. However, the complexity experimental challenges capturing early stages of development, ethical concerns associated with human embryo fetal research, limit our understanding how these affect brain organogenesis. Human cerebral organoids (hCO) attractive models due their ability model important regions transcriptomics vivo development. Furthermore, they provide three-dimensional environments that better mimic environment. To date, have been used understand effects genetics soluble on Establishing links between spatial hCO development will require new approaches. ResultsHere, we investigated geometric confinements transcriptomic changes during differentiation. Using a custom tunable agarose microwell platform generated embryoid bodies (EB) diverse shapes then further differentiated those EBs whole hCOs. Our results showed microwells did not negative gross impacts hCOs differentiate generally towards neural fates, there were clear dependent lineage specification. In particular, observed non-spherical signs altered neurodevelopmental kinetics favored medial ganglionic eminence-associated types over cortical regions. ConclusionsThe findings presented here suggest role for region specification Understanding patterning only improve but also handles which advance control systems vitro applications.