Alpha-Synuclein Expression in the Oligodendrocyte Lineage: an In Vitro and In Vivo Study Using Rodent and Human Models
| Autor: | Stefano Goldwurm, Antonio Boza-Serrano, Carla Azevedo, Staffan Holmqvist, Jonas Frisén, Tomas Deierborg, Mehdi Djelloul, Maggie S. Y. Yeung, Laurent Roybon |
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| Přispěvatelé: | Holmqvist, Staffan [0000-0001-6709-6666], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Cellular differentiation
SOX10 Induced Pluripotent Stem Cells Biology Biochemistry chemistry.chemical_compound Mice Neural Stem Cells Species Specificity Report Genetics medicine Animals Humans Cell Lineage Progenitor cell Induced pluripotent stem cell lcsh:QH301-705.5 Cells Cultured Embryonic Stem Cells Alpha-synuclein lcsh:R5-920 Cell Differentiation Cell Biology Embryonic stem cell Neural stem cell Oligodendrocyte Cell biology Oligodendroglia medicine.anatomical_structure lcsh:Biology (General) chemistry Immunology alpha-Synuclein lcsh:Medicine (General) Cell and Molecular Biology Developmental Biology |
| Zdroj: | Stem Cell Reports; 5(2), pp 174-184 (2015) Stem Cell Reports Stem Cell Reports, Vol 5, Iss 2, Pp 174-184 (2015) |
| ISSN: | 2213-6711 |
| Popis: | Summary In this study, we sought evidence for alpha-synuclein (ASYN) expression in oligodendrocytes, as a possible endogenous source of ASYN to explain its presence in glial inclusions found in multiple system atrophy (MSA) and Parkinson’s disease (PD). We identified ASYN in oligodendrocyte lineage progenitors isolated from the rodent brain, in oligodendrocytes generated from embryonic stem cells, and in induced pluripotent stem cells produced from fibroblasts of a healthy individual and patients diagnosed with MSA or PD, in cultures in vitro. Notably, we observed a significant decrease in ΑSYN during oligodendrocyte maturation. Additionally, we show the presence of transcripts in PDGFRΑ/CD140a+ cells and SOX10+ oligodendrocyte lineage nuclei isolated by FACS from rodent and human healthy and diseased brains, respectively. Our work identifies ASYN in oligodendrocyte lineage cells, and it offers additional in vitro cellular models that should provide significant insights of the functional implication of ASYN during oligodendrocyte development and disease. Graphical Abstract Highlights • ASYN is expressed during oligodendrocyte development • ASYN expression begins as early as PDGFRA+ oligodendrocyte lineage stage • SNCA transcripts are identified in oligodendrocyte lineage cells from the human brain • Human iPSCs provide cellular models for studying ASYN in oligodendrocytes The origin of ASYN present in glial inclusions in synucleinopathies is still elusive. In this article, Roybon and colleagues show that oligodendrocytes express the SNCA gene encoding for ASYN during their development. Their work establishes a strong basis for further understanding the functional implication of ASYN during oligodendrocyte development and disease, and it offers cellular models for modeling synucleionopathies. |
| Databáze: | OpenAIRE |
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