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

Fiorenzano, Alessandro LU ; Sozzi, Edoardo LU orcid ; Birtele, Marcella LU orcid ; Kajtez, Janko LU orcid ; Giacomoni, Jessica LU ; Nilsson, Fredrik LU orcid ; Bruzelius, Andreas LU ; Sharma, Yogita LU ; Zhang, Yu LU orcid and Mattsson, Bengt LU , et al. (2021) In Nature Communications 12(1).
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
12
issue
1
article number
7302
publisher
Nature Publishing Group
external identifiers
  • pmid:34911939
  • scopus:85121340549
ISSN
2041-1723
DOI
10.1038/s41467-021-27464-5
language
English
LU publication?
yes
id
626c7cd4-e450-4275-9e2a-707212c358c3
date added to LUP
2022-01-26 17:26:28
date last changed
2025-01-28 01:26:40
@article{626c7cd4-e450-4275-9e2a-707212c358c3,
  abstract     = {{<p>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.</p>}},
  author       = {{Fiorenzano, Alessandro and Sozzi, Edoardo and Birtele, Marcella and Kajtez, Janko and Giacomoni, Jessica and Nilsson, Fredrik and Bruzelius, Andreas and Sharma, Yogita and Zhang, Yu and Mattsson, Bengt and Emnéus, Jenny and Ottosson, Daniella Rylander and Storm, Petter and Parmar, Malin}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Single-cell transcriptomics captures features of human midbrain development and dopamine neuron diversity in brain organoids}},
  url          = {{http://dx.doi.org/10.1038/s41467-021-27464-5}},
  doi          = {{10.1038/s41467-021-27464-5}},
  volume       = {{12}},
  year         = {{2021}},
}