Viral mediated knockdown of GATA6 in SMA iPSC-derived astrocytes prevents motor neuron loss and microglial activation.

ABSTRACT: 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

SUBMITTER: Allison RL 

PROVIDER: S-EPMC9303278 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature