Single Cell Transcriptomics Identifies Stem Cell-Derived Graft Composition in a Model of Parkinson’s Disease
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA485495 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7669370.fastq.gz | Fastqsanger.gz | |||
| SRR7669380.fastq.gz | Fastqsanger.gz | |||
| SRR7669390.fastq.gz | Fastqsanger.gz | |||
| SRR7669400.fastq.gz | Fastqsanger.gz | |||
| SRR7669410.fastq.gz | Fastqsanger.gz |
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Project description:Single cell transcriptomics identifies stem cell-derived graft composition in a model of Parkinson’s disease.
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Project description: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.
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Project description:Molecular barcodes and single cell transcriptomics to map graft diversity and lineage of human DA neurons in a rat xenograft model of Parkinson’s Disease
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Project description:Stem cell treatments for neurodegenerative diseases are expected to reach clinical trials soon. Most of the approaches currently under development involve transplantation of immature progenitors that subsequently undergo phenotypic and functional maturation in vivo, and predicting the long term graft outcome already at the progenitor stage remains a challenge. Here, we took an unbiased approach to identify predictive markers expressed in dopamine neuron progenitors that correlate with graft outcome in an animal model of Parkinson's disease through gene expression analysis of >30 batches of grafted hESC-derived progenitors. We found that many of the commonly-used markers did not accurately predict in vivo subtype-specific maturation. Instead, we identified a specific set of markers associated with the caudal midbrain that correlate with high dopaminergic yield after transplantation in vivo. Using these markers, we developed a GMP differentiation protocol for highly efficient and reproducible production of transplantable dopamine progenitors from hESCs.
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