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 - 2020/12/1
Y1 - 2020/12/1
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 - Journal article
C2 - 32415072
AN - SCOPUS:85084707734
VL - 11
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 2434
ER -