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

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, Hilda Lundén-Miguel, Nikolaos Volakakis, Agnete Kirkeby, Thomas Perlmann () and Malin Parmar ()
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Katarína Tiklová: Ludwig Institute for Cancer Research
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
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
Thomas Perlmann: Ludwig Institute for Cancer Research
Malin Parmar: Lund University

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-16225-5

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