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

Alessandro Fiorenzano (), Edoardo Sozzi, Marcella Birtele, Janko Kajtez, Jessica Giacomoni, Fredrik Nilsson, Andreas Bruzelius, Yogita Sharma, Yu Zhang, Bengt Mattsson, Jenny Emnéus, Daniella Rylander Ottosson, Petter Storm and Malin Parmar
Additional contact information
Alessandro Fiorenzano: Lund University
Edoardo Sozzi: Lund University
Marcella Birtele: Lund University
Janko Kajtez: Lund University
Jessica Giacomoni: Lund University
Fredrik Nilsson: Lund University
Andreas Bruzelius: Lund University
Yogita Sharma: Lund University
Yu Zhang: Lund University
Bengt Mattsson: Lund University
Jenny Emnéus: Technical University of Denmark
Daniella Rylander Ottosson: Lund University
Petter Storm: Lund University
Malin Parmar: Lund University

Nature Communications, 2021, vol. 12, issue 1, 1-19

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

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27464-5

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DOI: 10.1038/s41467-021-27464-5

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