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

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 purified  murine wildtype astrocyte cultures (untreated and treated with IL-6 or EphB1).

星形胶质细胞(Astrocyte)对神经元损伤的应答可对神经元恢复产生有益或有害影响，但调控此类差异化应答的机制仍知之甚少。转录组分析结果显示，EphB1可在星形胶质细胞中诱导出保护性炎症特征，该特征与白细胞介素(IL)-6所诱导的应答存在显著差异——已知IL-6同时具备促炎与抗炎双重特性。本研究证实，这种由EphB1介导的有益信号通路，在源自肌萎缩侧索硬化症(ALS)患者的人类诱导多能干细胞(iPSC)衍生星形胶质细胞中遭到破坏。本数据集包含经纯化的小鼠野生型星形胶质细胞培养物的全转录组基因表达谱，这些培养物分为未经处理组、经IL-6处理组以及经EphB1处理组。