Viral mediated knockdown of GATA6 in SMA iPSC ‐derived astrocytes prevents motor neuron loss and microglial activation
| العنوان: | Viral mediated knockdown of |
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| المؤلفون: | Reilly L. Allison, Emily Welby, Guzal Khayrullina, Barrington G. Burnett, Allison D. Ebert |
| المصدر: | Glia. 70:989-1004 |
| بيانات النشر: | Wiley, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Motor Neurons, Induced Pluripotent Stem Cells, Survival of Motor Neuron 1 Protein, Muscular Atrophy, Spinal, Disease Models, Animal, Cellular and Molecular Neuroscience, Neurology, Astrocytes, GATA6 Transcription Factor, Nerve Degeneration, Animals, Humans, Microglia, Child |
| الوصف: | Spinal muscular atrophy (SMA), a pediatric genetic disorder, is characterized by the profound loss of spinal cord motor neurons and subsequent muscle atrophy and death. Although the mechanisms underlying motor neuron loss are not entirely clear, data from our work and others support the idea that glial cells contribute to disease pathology. GATA6, a transcription factor that we have previously shown to be upregulated in SMA astrocytes, is negatively regulated by SMN (survival motor neuron) and can increase the expression of inflammatory regulator NFκB. In this study, we identified upregulated GATA6 as a contributor to increased activation, pro-inflammatory ligand production, and neurotoxicity in spinal-cord patterned astrocytes differentiated from SMA patient induced pluripotent stem cells. Reducing GATA6 expression in SMA astrocytes via lentiviral infection ameliorated these effects to healthy control levels. Additionally, we found that SMA astrocytes contribute to SMA microglial phagocytosis, which was again decreased by lentiviral-mediated knockdown of GATA6. Together these data identify a role of GATA6 in SMA astrocyte pathology and further highlight glia as important targets of therapeutic intervention in SMA. |
| تدمد: | 1098-1136 0894-1491 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::afd3b375581d723c39ce9da62f4bbcd5 https://doi.org/10.1002/glia.24153 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....afd3b375581d723c39ce9da62f4bbcd5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10981136 08941491 |
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