Single-cell transcriptomics captures features of human midbrain development and dopamine neuron diversity in brain organoids

• DOI: 10.1038/s41467-021-27464-5
• Publication Date: 2021-12-15T11:05:44Z
• Authors: Alessandro Fioren...; Edoardo Sozzi; Marcella Birtele; Janko Kajtez; Jessica Giacomoni; Fredrik Nilsson; Andreas Bruzelius; Yogita Sharma; Yu Zhang; Bengt Mattsson; Jenny Emnéus; Daniella Rylander...; Petter Storm; Malin Parmar
• Keywords: Organoid; Human brain

Abstract Three-dimensional brain organoids have emerged as a valuable model system for studies of human development and pathology. Here we establish midbrain organoid culture to study the developmental trajectory from pluripotent stem cells mature dopamine neurons. Using single cell RNA sequencing, identify presence three molecularly distinct subtypes neurons with high similarity those in developing adult midbrain. However, despite significant advancements field, use can be limited by issues reproducibility incomplete maturation which was also observed this study. We therefore designed bioengineered ventral supported recombinant spider-silk microfibers functionalized full-length laminin. show that silk reproduce key molecular aspects neurogenesis reduce inter-organoid variability terms type composition neuron formation.