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Single-cell transcriptional and functional analysis of dopaminergic neurons in organoid-like cultures derived from human fetal midbrain

Birtele, Marcella LU orcid ; Storm, Petter LU orcid ; Sharma, Yogita LU ; Kajtez, Janko LU orcid ; Wahlestedt, Jenny Nelander LU orcid ; Sozzi, Edoardo LU orcid ; Nilsson, Fredrik LU orcid ; Stott, Simon LU ; He, Xiaoling L and Mattsson, Bengt LU , et al. (2022) In Development: For advances in developmental biology and stem cells 149(23).
Abstract

Significant efforts are ongoing to develop refined differentiation protocols to generate midbrain dopamine (DA) neurons from pluripotent stem cells (PSCs) for application in disease modeling, diagnostics, drug screening, and cell-based therapies for Parkinson's Disease (PD). An increased understanding of the timing and molecular mechanisms promoting the generation of distinct subtypes of human midbrain DA during development will be essential for guiding future efforts to generate molecularly defined and subtype-specific DA neurons from PSCs. Here, we used droplet-based single-cell RNA sequencing to transcriptionally profile the developing human ventral midbrain (VM) when the DA neurons are generated (6-11 weeks post-conception) and... (More)

Significant efforts are ongoing to develop refined differentiation protocols to generate midbrain dopamine (DA) neurons from pluripotent stem cells (PSCs) for application in disease modeling, diagnostics, drug screening, and cell-based therapies for Parkinson's Disease (PD). An increased understanding of the timing and molecular mechanisms promoting the generation of distinct subtypes of human midbrain DA during development will be essential for guiding future efforts to generate molecularly defined and subtype-specific DA neurons from PSCs. Here, we used droplet-based single-cell RNA sequencing to transcriptionally profile the developing human ventral midbrain (VM) when the DA neurons are generated (6-11 weeks post-conception) and their subsequent differentiation into functional mature DA neurons in primary fetal 3D organoid-like cultures. This approach revealed that 3D cultures are superior to monolayer conditions for their ability to generate and maintain mature DA neurons; hence they have the potential to be used for studying human VM development. These results provide a unique transcriptional profile of the developing human fetal VM and functionally mature human DA neurons, which can be used to guide stem cell-based therapies and disease modeling approaches in PD.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Development: For advances in developmental biology and stem cells
volume
149
issue
23
article number
dev200504
publisher
The Company of Biologists Ltd
external identifiers
  • pmid:36305490
  • scopus:85149130315
ISSN
1477-9129
DOI
10.1242/dev.200504
language
English
LU publication?
yes
additional info
© 2022. Published by The Company of Biologists Ltd.
id
85b57c5e-07fa-4b50-9f51-719d53ae7d85
date added to LUP
2022-12-07 08:57:52
date last changed
2024-07-09 21:51:32
@article{85b57c5e-07fa-4b50-9f51-719d53ae7d85,
  abstract     = {{<p>Significant efforts are ongoing to develop refined differentiation protocols to generate midbrain dopamine (DA) neurons from pluripotent stem cells (PSCs) for application in disease modeling, diagnostics, drug screening, and cell-based therapies for Parkinson's Disease (PD). An increased understanding of the timing and molecular mechanisms promoting the generation of distinct subtypes of human midbrain DA during development will be essential for guiding future efforts to generate molecularly defined and subtype-specific DA neurons from PSCs. Here, we used droplet-based single-cell RNA sequencing to transcriptionally profile the developing human ventral midbrain (VM) when the DA neurons are generated (6-11 weeks post-conception) and their subsequent differentiation into functional mature DA neurons in primary fetal 3D organoid-like cultures. This approach revealed that 3D cultures are superior to monolayer conditions for their ability to generate and maintain mature DA neurons; hence they have the potential to be used for studying human VM development. These results provide a unique transcriptional profile of the developing human fetal VM and functionally mature human DA neurons, which can be used to guide stem cell-based therapies and disease modeling approaches in PD.</p>}},
  author       = {{Birtele, Marcella and Storm, Petter and Sharma, Yogita and Kajtez, Janko and Wahlestedt, Jenny Nelander and Sozzi, Edoardo and Nilsson, Fredrik and Stott, Simon and He, Xiaoling L and Mattsson, Bengt and Ottosson, Daniella Rylander and Barker, Roger A and Fiorenzano, Alessandro and Parmar, Malin}},
  issn         = {{1477-9129}},
  language     = {{eng}},
  number       = {{23}},
  publisher    = {{The Company of Biologists Ltd}},
  series       = {{Development: For advances in developmental biology and stem cells}},
  title        = {{Single-cell transcriptional and functional analysis of dopaminergic neurons in organoid-like cultures derived from human fetal midbrain}},
  url          = {{http://dx.doi.org/10.1242/dev.200504}},
  doi          = {{10.1242/dev.200504}},
  volume       = {{149}},
  year         = {{2022}},
}