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Deconvolution of spatial sequencing provides accurate characterization of hESC-derived DA transplants in vivo.

Rájová, Jana LU ; Davidsson, Marcus LU ; Avallone, Martino LU ; Hartnor, Morgan ; Aldrin-Kirk, Patrick LU ; Cardoso, Tiago LU ; Nolbrant, Sara LU ; Mollbrink, Annelie ; Storm, Petter LU orcid and Heuer, Andreas LU , et al. (2023) In Molecular Therapy - Methods and Clinical Development 29. p.381-394
Abstract

Cell therapy for Parkinson's disease has experienced substantial growth in the past decades with several ongoing clinical trials. Despite increasing refinement of differentiation protocols and standardization of the transplanted neural precursors, the transcriptomic analysis of cells in the transplant after its full maturation
in vivo has not been thoroughly investigated. Here, we present spatial transcriptomics analysis of fully differentiated grafts in their host tissue. Unlike earlier transcriptomics analyses using single-cell technologies, we observe that cells derived from human embryonic stem cells (hESCs) in the grafts adopt mature dopaminergic signatures. We show that the presence of phenotypic dopaminergic genes, which... (More)

Cell therapy for Parkinson's disease has experienced substantial growth in the past decades with several ongoing clinical trials. Despite increasing refinement of differentiation protocols and standardization of the transplanted neural precursors, the transcriptomic analysis of cells in the transplant after its full maturation
in vivo has not been thoroughly investigated. Here, we present spatial transcriptomics analysis of fully differentiated grafts in their host tissue. Unlike earlier transcriptomics analyses using single-cell technologies, we observe that cells derived from human embryonic stem cells (hESCs) in the grafts adopt mature dopaminergic signatures. We show that the presence of phenotypic dopaminergic genes, which were found to be differentially expressed in the transplants, is concentrated toward the edges of the grafts, in agreement with the immunohistochemical analyses. Deconvolution shows dopamine neurons being the dominating cell type in many features beneath the graft area. These findings further support the preferred environmental niche of TH-positive cells and confirm their dopaminergic phenotype through the presence of multiple dopaminergic markers.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Therapy - Methods and Clinical Development
volume
29
pages
381 - 394
publisher
Nature Publishing Group
external identifiers
  • pmid:37251982
  • scopus:85159628613
ISSN
2329-0501
DOI
10.1016/j.omtm.2023.04.008
language
English
LU publication?
yes
additional info
© 2023 The Author(s).
id
eed44c51-fd44-4021-a47a-50b1791b39e3
date added to LUP
2023-07-07 14:05:15
date last changed
2024-11-30 22:50:58
@article{eed44c51-fd44-4021-a47a-50b1791b39e3,
  abstract     = {{<p>Cell therapy for Parkinson's disease has experienced substantial growth in the past decades with several ongoing clinical trials. Despite increasing refinement of differentiation protocols and standardization of the transplanted neural precursors, the transcriptomic analysis of cells in the transplant after its full maturation<br>
 in vivo has not been thoroughly investigated. Here, we present spatial transcriptomics analysis of fully differentiated grafts in their host tissue. Unlike earlier transcriptomics analyses using single-cell technologies, we observe that cells derived from human embryonic stem cells (hESCs) in the grafts adopt mature dopaminergic signatures. We show that the presence of phenotypic dopaminergic genes, which were found to be differentially expressed in the transplants, is concentrated toward the edges of the grafts, in agreement with the immunohistochemical analyses. Deconvolution shows dopamine neurons being the dominating cell type in many features beneath the graft area. These findings further support the preferred environmental niche of TH-positive cells and confirm their dopaminergic phenotype through the presence of multiple dopaminergic markers.<br>
 </p>}},
  author       = {{Rájová, Jana and Davidsson, Marcus and Avallone, Martino and Hartnor, Morgan and Aldrin-Kirk, Patrick and Cardoso, Tiago and Nolbrant, Sara and Mollbrink, Annelie and Storm, Petter and Heuer, Andreas and Parmar, Malin and Björklund, Tomas}},
  issn         = {{2329-0501}},
  language     = {{eng}},
  month        = {{06}},
  pages        = {{381--394}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Molecular Therapy - Methods and Clinical Development}},
  title        = {{Deconvolution of spatial sequencing provides accurate characterization of hESC-derived DA transplants 
        in vivo.}},
  url          = {{http://dx.doi.org/10.1016/j.omtm.2023.04.008}},
  doi          = {{10.1016/j.omtm.2023.04.008}},
  volume       = {{29}},
  year         = {{2023}},
}