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

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Single cell transcriptomics identifies stem cell-derived graft composition in a model of Parkinson’s disease. / Tiklová, Katarína; Nolbrant, Sara; Fiorenzano, Alessandro; Björklund, Åsa K.; Sharma, Yogita; Heuer, Andreas; Gillberg, Linda; Hoban, Deirdre B.; Cardoso, Tiago; Adler, Andrew F.; Birtele, Marcella; Lundén-Miguel, Hilda; Volakakis, Nikolaos; Kirkeby, Agnete; Perlmann, Thomas; Parmar, Malin.

I: Nature Communications, Vol. 11, Nr. 1, 2434, 2020.

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Tiklová, Katarína ; Nolbrant, Sara ; Fiorenzano, Alessandro ; Björklund, Åsa K. ; Sharma, Yogita ; Heuer, Andreas ; Gillberg, Linda ; Hoban, Deirdre B. ; Cardoso, Tiago ; Adler, Andrew F. ; Birtele, Marcella ; Lundén-Miguel, Hilda ; Volakakis, Nikolaos ; Kirkeby, Agnete ; Perlmann, Thomas ; Parmar, Malin. / Single cell transcriptomics identifies stem cell-derived graft composition in a model of Parkinson’s disease. I: Nature Communications. 2020 ; Vol. 11, Nr. 1.

RIS

TY - JOUR

T1 - Single cell transcriptomics identifies stem cell-derived graft composition in a model of Parkinson’s disease

AU - Tiklová, Katarína

AU - Nolbrant, Sara

AU - Fiorenzano, Alessandro

AU - Björklund, Åsa K.

AU - Sharma, Yogita

AU - Heuer, Andreas

AU - Gillberg, Linda

AU - Hoban, Deirdre B.

AU - Cardoso, Tiago

AU - Adler, Andrew F.

AU - Birtele, Marcella

AU - Lundén-Miguel, Hilda

AU - Volakakis, Nikolaos

AU - Kirkeby, Agnete

AU - Perlmann, Thomas

AU - Parmar, Malin

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-020-16225-5

DO - 10.1038/s41467-020-16225-5

M3 - Article

VL - 11

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 2434

ER -