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

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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review


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.

Sidor (från-till)381-394
TidskriftMolecular Therapy - Methods and Clinical Development
StatusPublished - 2023 juni 8

Bibliografisk information

© 2023 The Author(s).

Ämnesklassifikation (UKÄ)

  • Cell- och molekylärbiologi


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