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Single cell transcriptomics identifies stem cell-derived graft composition in a model of Parkinson’s disease

Author

Listed:
  • Katarína Tiklová

    (Ludwig Institute for Cancer Research
    Karolinska Institutet)

  • Sara Nolbrant

    (Lund University)

  • Alessandro Fiorenzano

    (Lund University)

  • Åsa K. Björklund

    (Uppsala University)

  • Yogita Sharma

    (Lund University)

  • Andreas Heuer

    (Lund University)

  • Linda Gillberg

    (Ludwig Institute for Cancer Research
    Karolinska Institutet)

  • Deirdre B. Hoban

    (Lund University)

  • Tiago Cardoso

    (Lund University)

  • Andrew F. Adler

    (Lund University)

  • Marcella Birtele

    (Lund University)

  • Hilda Lundén-Miguel

    (Ludwig Institute for Cancer Research)

  • Nikolaos Volakakis

    (Ludwig Institute for Cancer Research)

  • Agnete Kirkeby

    (Lund University
    University of Copenhagen)

  • Thomas Perlmann

    (Ludwig Institute for Cancer Research
    Karolinska Institutet)

  • Malin Parmar

    (Lund University)

Abstract

Cell replacement is a long-standing and realistic goal for the treatment of Parkinsonʼs disease (PD). Cells for transplantation can be obtained from fetal brain tissue or from stem cells. However, after transplantation, dopamine (DA) neurons are seen to be a minor component of grafts, and it has remained difficult to determine the identity of other cell types. Here, we report analysis by single-cell RNA sequencing (scRNA-seq) combined with comprehensive histological analyses to characterize intracerebral grafts from human embryonic stem cells (hESCs) and fetal tissue after functional maturation in a pre-clinical rat PD model. We show that neurons and astrocytes are major components in both fetal and stem cell-derived grafts. Additionally, we identify a cell type closely resembling a class of recently identified perivascular-like cells in stem cell-derived grafts. Thus, this study uncovers previously unknown cellular diversity in a clinically relevant cell replacement PD model.

Suggested Citation

  • Katarína Tiklová & Sara Nolbrant & Alessandro Fiorenzano & Åsa K. Björklund & Yogita Sharma & Andreas Heuer & Linda Gillberg & Deirdre B. Hoban & Tiago Cardoso & Andrew F. Adler & Marcella Birtele & H, 2020. "Single cell transcriptomics identifies stem cell-derived graft composition in a model of Parkinson’s disease," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16225-5
    DOI: 10.1038/s41467-020-16225-5
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