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Lineage tracing of stem cell-derived dopamine grafts in a Parkinson's model reveals shared origin of all graft-derived cells

Storm, Petter LU orcid ; Zhang, Yu LU orcid ; Nilsson, Fredrik LU orcid ; Fiorenzano, Alessandro LU ; Krausse, Niklas LU ; Åkerblom, Malin LU ; Davidsson, Marcus LU ; Yuan, Joan LU orcid ; Kirkeby, Agnete LU and Björklund, Tomas LU orcid , et al. (2024) In Science Advances 10(42). p.1-14
Abstract

Stem cell therapies for Parkinson's disease are at an exciting time of development, and several clinical trials have recently been initiated. Human pluripotent stem cells are differentiated into transplantable dopamine (DA) progenitors which are proliferative at the time of grafting and undergo terminal differentiation and maturation in vivo. While the progenitors are homogeneous at the time of transplantation, they give rise to heterogeneous grafts composed not only of therapeutic DA neurons but also of other mature cell types. The mechanisms for graft diversification are unclear. We used single-nucleus RNA-seq and ATAC-seq to profile DA progenitors before transplantation combined with molecular barcode-based tracing to determine... (More)

Stem cell therapies for Parkinson's disease are at an exciting time of development, and several clinical trials have recently been initiated. Human pluripotent stem cells are differentiated into transplantable dopamine (DA) progenitors which are proliferative at the time of grafting and undergo terminal differentiation and maturation in vivo. While the progenitors are homogeneous at the time of transplantation, they give rise to heterogeneous grafts composed not only of therapeutic DA neurons but also of other mature cell types. The mechanisms for graft diversification are unclear. We used single-nucleus RNA-seq and ATAC-seq to profile DA progenitors before transplantation combined with molecular barcode-based tracing to determine origin and shared lineages of the mature cell types in the grafts. Our data demonstrate that astrocytes, vascular leptomeningeal cells, and DA neurons are the main component of the DAergic grafts, originating from a common progenitor that is tripotent at the time of transplantation.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Parkinson Disease/metabolism, Cell Lineage/genetics, Animals, Dopaminergic Neurons/metabolism, Humans, Cell Differentiation, Stem Cell Transplantation/methods, Mice, Dopamine/metabolism, Disease Models, Animal, Astrocytes/metabolism
in
Science Advances
volume
10
issue
42
article number
eadn3057
pages
1 - 14
publisher
American Association for the Advancement of Science (AAAS)
external identifiers
  • scopus:85206844329
  • pmid:39423273
ISSN
2375-2548
DOI
10.1126/sciadv.adn3057
language
English
LU publication?
yes
id
51986f93-4869-461a-87a8-025165367951
date added to LUP
2024-12-09 11:04:00
date last changed
2025-07-23 11:01:40
@article{51986f93-4869-461a-87a8-025165367951,
  abstract     = {{<p>Stem cell therapies for Parkinson's disease are at an exciting time of development, and several clinical trials have recently been initiated. Human pluripotent stem cells are differentiated into transplantable dopamine (DA) progenitors which are proliferative at the time of grafting and undergo terminal differentiation and maturation in vivo. While the progenitors are homogeneous at the time of transplantation, they give rise to heterogeneous grafts composed not only of therapeutic DA neurons but also of other mature cell types. The mechanisms for graft diversification are unclear. We used single-nucleus RNA-seq and ATAC-seq to profile DA progenitors before transplantation combined with molecular barcode-based tracing to determine origin and shared lineages of the mature cell types in the grafts. Our data demonstrate that astrocytes, vascular leptomeningeal cells, and DA neurons are the main component of the DAergic grafts, originating from a common progenitor that is tripotent at the time of transplantation.</p>}},
  author       = {{Storm, Petter and Zhang, Yu and Nilsson, Fredrik and Fiorenzano, Alessandro and Krausse, Niklas and Åkerblom, Malin and Davidsson, Marcus and Yuan, Joan and Kirkeby, Agnete and Björklund, Tomas and Parmar, Malin}},
  issn         = {{2375-2548}},
  keywords     = {{Parkinson Disease/metabolism; Cell Lineage/genetics; Animals; Dopaminergic Neurons/metabolism; Humans; Cell Differentiation; Stem Cell Transplantation/methods; Mice; Dopamine/metabolism; Disease Models, Animal; Astrocytes/metabolism}},
  language     = {{eng}},
  month        = {{10}},
  number       = {{42}},
  pages        = {{1--14}},
  publisher    = {{American Association for the Advancement of Science (AAAS)}},
  series       = {{Science Advances}},
  title        = {{Lineage tracing of stem cell-derived dopamine grafts in a Parkinson's model reveals shared origin of all graft-derived cells}},
  url          = {{http://dx.doi.org/10.1126/sciadv.adn3057}},
  doi          = {{10.1126/sciadv.adn3057}},
  volume       = {{10}},
  year         = {{2024}},
}