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

Autor:	Tiklová K; Ludwig Institute for Cancer Research, Box 240, SE-171 77, Stockholm, Sweden.; Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77, Stockholm, Sweden., Nolbrant S; Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, and Lund Stem Cell Centre, Department of Experimental Medical Science, Lund University, 22184, Lund, Sweden., Fiorenzano A; Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, and Lund Stem Cell Centre, Department of Experimental Medical Science, Lund University, 22184, Lund, Sweden., Björklund ÅK; Department of Cell and Molecular Biology, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Uppsala University, Husargatan 3, SE-752 37, Uppsala, Sweden., Sharma Y; Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, and Lund Stem Cell Centre, Department of Experimental Medical Science, Lund University, 22184, Lund, Sweden., Heuer A; Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, and Lund Stem Cell Centre, Department of Experimental Medical Science, Lund University, 22184, Lund, Sweden., Gillberg L; Ludwig Institute for Cancer Research, Box 240, SE-171 77, Stockholm, Sweden.; Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77, Stockholm, Sweden., Hoban DB; Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, and Lund Stem Cell Centre, Department of Experimental Medical Science, Lund University, 22184, Lund, Sweden., Cardoso T; Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, and Lund Stem Cell Centre, Department of Experimental Medical Science, Lund University, 22184, Lund, Sweden., Adler AF; Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, and Lund Stem Cell Centre, Department of Experimental Medical Science, Lund University, 22184, Lund, Sweden., Birtele M; Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, and Lund Stem Cell Centre, Department of Experimental Medical Science, Lund University, 22184, Lund, Sweden., Lundén-Miguel H; Ludwig Institute for Cancer Research, Box 240, SE-171 77, Stockholm, Sweden., Volakakis N; Ludwig Institute for Cancer Research, Box 240, SE-171 77, Stockholm, Sweden., Kirkeby A; Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, and Lund Stem Cell Centre, Department of Experimental Medical Science, Lund University, 22184, Lund, Sweden.; Novo Nordisk Foundation Center for Stem Cell Biology (DanStem), University of Copenhagen, 2200, Copenhagen, Denmark., Perlmann T; Ludwig Institute for Cancer Research, Box 240, SE-171 77, Stockholm, Sweden. thomas.perlmann@ki.se.; Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77, Stockholm, Sweden. thomas.perlmann@ki.se., Parmar M; Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, and Lund Stem Cell Centre, Department of Experimental Medical Science, Lund University, 22184, Lund, Sweden. malin.parmar@med.lu.se.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2020 May 15; Vol. 11 (1), pp. 2434. Date of Electronic Publication: 2020 May 15.
DOI:	10.1038/s41467-020-16225-5
Abstrakt:	Cell replacement is a long-standing and realistic goal for the treatment of Parkinson's 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.
Databáze:	MEDLINE
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