Neuronal EphB1 induces STAT3 activation in astrocytes, which is impaired in ALS models [Hs]

Astrocyte  responses to neuronal injury may be beneficial or detrimental to neuronal recovery, but the mechanism that determines these different responses are poorly understood. Transcriptional analysis showed that EphB1 induces a protective inflammatory signature in astrocytes, which is distinct from the response evoked by interleukin (IL)-6, which is known to have both pro- and anti-inflammatory properties. We demonstrate that this beneficial EphB1 induced signaling pathway is disrupted in astrocytes derived from human induced pluripotent stem cells (iPSC) of amyotrophic lateral sclerosis (ALS) patients. Examination of transcriptome-wide gene expression profiles of terminally differentiated and enriched iPSC-derived astrocytes harboring the SOD1 D90A mutation.