Efficient and Scalable Generation of Human Ventral Midbrain Astrocytes from Human-Induced Pluripotent Stem Cells
| Autor: | Sarah F. McComish, Maeve A. Caldwell, Petros Stathakos, Lucy A. Crompton, Oscar Cordero-Llana, Jon D. Lane |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Parkinson's disease
General Chemical Engineering Induced Pluripotent Stem Cells Biology General Biochemistry Genetics and Molecular Biology neuroinflammation Midbrain astrocyte Mesencephalon Dopamine medicine Humans Induced pluripotent stem cell Neuroinflammation General Immunology and Microbiology Microglia Dopaminergic Neurons General Neuroscience Neurodegeneration ventral midbrain differentiation medicine.disease medicine.anatomical_structure reactive human induced pluripotent stem cell Astrocytes Neuroscience Astrocyte medicine.drug |
| Zdroj: | Crompton, L A, McComish, S F, Stathakos, P, Cordero Llana, O, Lane, J D & Caldwell, M A 2021, ' Efficient and Scalable Generation of Human Ventral Midbrain Astrocytes from Human-Induced Pluripotent Stem Cells ', Journal of Visualized Experiments, no. 176, e62095 . https://doi.org/10.3791/62095 |
| Popis: | In Parkinson's disease, progressive dysfunction and degeneration of dopamine neurons in the ventral midbrain cause life-changing symptoms. Neuronal degeneration has diverse causes in Parkinson's, including non-cell autonomous mechanisms mediated by astrocytes. Throughout the CNS, astrocytes are essential for neuronal survival and function, as they maintain metabolic homeostasis in the neural environment. Astrocytes interact with the immune cells of the CNS, microglia, to modulate neuroinflammation, which is observed from the earliest stages of Parkinson's, and has a direct impact on the progression of its pathology. In diseases with a chronic neuroinflammatory element, including Parkinson's, astrocytes acquire a neurotoxic phenotype, and thus enhance neurodegeneration. Consequently, astrocytes are a potential therapeutic target to slow or halt disease, but this will require a deeper understanding of their properties and roles in Parkinson's. Accurate models of human ventral midbrain astrocytes for in vitro study are therefore urgently required.We have developed a protocol to generate high purity cultures of ventral midbrain-specific astrocytes (vmAstros) from hiPSCs that can be used for Parkinson's research. vmAstros can be routinely produced from multiple hiPSC lines, and express specific astrocytic and ventral midbrain markers. This protocol is scalable, and thus suitable for high-throughput applications, including for drug screening. Crucially, the hiPSC derived-vmAstros demonstrate immunomodulatory characteristics typical of their in vivo counterparts, enabling mechanistic studies of neuroinflammatory signaling in Parkinson's. |
| Databáze: | OpenAIRE |
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