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Martino Avallone

Martino Avallone

Doctoral student

Martino Avallone

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

Author

  • Jana Rájová
  • Marcus Davidsson
  • Martino Avallone
  • Morgan Hartnor
  • Patrick Aldrin-Kirk
  • Tiago Cardoso
  • Sara Nolbrant
  • Annelie Mollbrink
  • Petter Storm
  • Andreas Heuer
  • Malin Parmar
  • Tomas Björklund

Summary, in English

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.

Department/s

  • LTH Profile Area: Engineering Health
  • Molecular Neuromodulation
  • MultiPark: Multidisciplinary research focused on Parkinson´s disease
  • Behavioural Neuroscience Laboratory
  • Developmental and Regenerative Neurobiology
  • StemTherapy: National Initiative on Stem Cells for Regenerative Therapy

Publishing year

2023-06-08

Language

English

Pages

381-394

Publication/Series

Molecular Therapy - Methods and Clinical Development

Volume

29

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Cell and Molecular Biology

Status

Published

Research group

  • Molecular Neuromodulation
  • Behavioural Neuroscience Laboratory
  • Developmental and Regenerative Neurobiology

ISBN/ISSN/Other

  • ISSN: 2329-0501