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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 NF\u03baB. In this study, we identified upregulated GATA6 as a contributor to increased activation, pro\u2010inflammatory ligand production, and neurotoxicity in spinal\u2010cord 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\u2010mediated 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.<\/jats:p>","DOI":"10.1002\/glia.24153","type":"journal-article","created":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T08:24:40Z","timestamp":1643358280000},"page":"989-1004","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Viral mediated knockdown of\n                    <scp>GATA6<\/scp>\n                    in\n                    <scp>SMA iPSC<\/scp>\n                    \u2010derived astrocytes prevents motor neuron loss and microglial activation"],"prefix":"10.1002","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0074-4099","authenticated-orcid":false,"given":"Reilly L.","family":"Allison","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Neurobiology, and Anatomy Medical College of Wisconsin  Milwaukee 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