Fig. 4

Translational relevance of the neurotoxic mechanism and hypothesis-generating mechanistic explanations. Contact-dependent experiments were pursued by co-culturing reactive ES-derived astrocytes stimulated with a panel of clinically relevant neuroinflammatory factors together with motor neurons (A). Following astrogliosis induced by IL-1β and IL-6, we saw the largest P–c-Jun upregulation (B), and a concordant astrocyte-mediated neurotoxic effect on motor neurons (C). Hypothesis-generating polyA + bulk-RNA-sequencing of FACS-sorted reactive astrocytes (D) demonstrated some tentative pathways possibly implicated in this (E–G), of which some are also implicated in the c-jun N terminal kinase pathway [95] (E). Significance level: NS, non-significant; *, p ≤ 0.05. Abbreviations: DAPI, 4’,6-diamidino-2-phenylindole dihydrochloride; ER, endoplasmic reticulum; eGFP, enhanced green fluorescent protein; Hb9, homeobox Hb9; IL-1α; IL-1β, interleukin 1β; IL-6, interleukin 6; P–c-Jun, phosphorylated c-Jun; TNF-α, tumor necrosis factor α. Scale bars: 100 μm