Single-cell transcriptomics of human iPSC differentiation dynamics reveal a core molecular network of Parkinson’s disease
| العنوان: | Single-cell transcriptomics of human iPSC differentiation dynamics reveal a core molecular network of Parkinson’s disease |
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| المؤلفون: | Gabriela Novak, Dimitrios Kyriakis, Kamil Grzyb, Michela Bernini, Sophie Rodius, Gunnar Dittmar, Steven Finkbeiner, Alexander Skupin |
| المصدر: | Communications Biology, Vol 5, Iss 1, Pp 1-19 (2022) Communications Biology Communications biology, vol 5, iss 1 |
| بيانات النشر: | Nature Portfolio, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Aging, QH301-705.5, Neurogenesis, Parkinson's disease, Induced Pluripotent Stem Cells, Cell death in the nervous system, Medicine (miscellaneous), Stem-cell differentiation, Neurodegenerative, General Biochemistry, Genetics and Molecular Biology, Article, Stem Cell Research - Nonembryonic - Human, Genetics, 2.1 Biological and endogenous factors, Humans, Aetiology, Biology (General), Parkinson's Disease, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Stem Cell Research - Induced Pluripotent Stem Cell, Sequence Analysis, RNA, Gene Expression Profiling, Neurosciences, Cell Differentiation, Parkinson Disease, Stem Cell Research, Brain Disorders, Differentiation, Neurological, Mutation, RNA, Single-Cell Analysis, General Agricultural and Biological Sciences, Transcriptome, Sequence Analysis, Protein Kinases, Biotechnology |
| الوصف: | Parkinson’s disease (PD) is the second-most prevalent neurodegenerative disorder, characterized by the loss of dopaminergic neurons (mDA) in the midbrain. The underlying mechanisms are only partly understood and there is no treatment to reverse PD progression. Here, we investigated the disease mechanism using mDA neurons differentiated from human induced pluripotent stem cells (hiPSCs) carrying the ILE368ASN mutation within the PINK1 gene, which is strongly associated with PD. Single-cell RNA sequencing (RNAseq) and gene expression analysis of a PINK1-ILE368ASN and a control cell line identified genes differentially expressed during mDA neuron differentiation. Network analysis revealed that these genes form a core network, members of which interact with all known 19 protein-coding Parkinson’s disease-associated genes. This core network encompasses key PD-associated pathways, including ubiquitination, mitochondrial function, protein processing, RNA metabolism, and vesicular transport. Proteomics analysis showed a consistent alteration in proteins of dopamine metabolism, indicating a defect of dopaminergic metabolism in PINK1-ILE368ASN neurons. Our findings suggest the existence of a network onto which pathways associated with PD pathology converge, and offers an inclusive interpretation of the phenotypic heterogeneity of PD. Gabriela Novak et al. utilize scRNA-seq to investigate expression profiles in iPSC-derived midbrain dopaminergic neurons from Parkinson’s disease patients or healthy controls. Their results suggest a core molecular network associated with Parkinson’s disease pathology, and provide a future resource for investigation of this critical disorder. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2399-3642 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1c9d642a5389f5622539205dacf2156aTest https://doaj.org/article/6696f50e07a34ed79076d449dc8df738Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1c9d642a5389f5622539205dacf2156a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23993642 |
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