Fig. 7

JAK2ca activates the JAK2-STAT3 pathway and induces astrocyte reactivity. a, WT mice were injected in the hippocampus with AAV-GFP alone (N = 6) or AAV-JAK2ca + AAV-GFP (JAK2ca + GFP, N = 6) at the same total viral titer and were studied 1–2 months later. b, Confocal images of hippocampal sections, stained for GFP (green) and STAT3 (cyan) in WT-GFP or WT-JAK2ca mice. JAK2ca induces STAT3 upregulation and nuclear accumulation in astrocytes, indicating STAT3 activation (arrowhead). c, STAT3 IR quantification in astrocyte nucleus from images in b. d, Representative low magnification images showing the transduced area (GFP⁺, green) and corresponding GFAP staining (magenta) in the hippocampus of WT-GFP and WT-JAK2ca mice. JAK2ca increases GFAP levels in a large part of the hippocampus (outlined). e, Confocal images of astrocytes stained for GFP (green), GFAP (magenta) and vimentin (red) in WT-GFP and WT-JAK2ca mice. JAK2ca increases GFAP and vimentin expression in hippocampal astrocytes and induces morphological changes. f, GFAP IR is increased by 70% in JAK2ca-injected hippocampus. g, Sholl analysis applied to GFAP-labelled astrocytes shows that reactive astrocytes in WT-JAK2ca mice have a larger domain area and a higher ramification index, a measure of cell complexity. h, RT-qPCR analysis was performed on acutely sorted hippocampal astrocytes from WT-GFP and WT-JAK2ca mice. Jak2, Gfap and Serpina3n are significantly overexpressed in WT-JAK2ca astrocytes. N = 7/group. c, f, g, Student t test. h, Gfap, Serpina3n: Student t test, Jak2: Mann-Whitney test. * p < 0.05, ** p < 0.01, *** p < 0.001