Extended Data Fig. 8: TGFβ drives CNS wound healing and resolution of inflammation, related to Fig. 4.

a, Intact fibroblast topography in uninjured cKO (Col1a2^creER; Tgfbr2^flox) parenchyma (insets: leptomeningeal/perivascular/periventricular fibroblasts). b, Lesional images showing ER-TR7 in controls or cKOs, 14dpi (tamoxifen as in Fig. 4d; dotted line shows lesion boundary). c-g, Quantification of 14dpi lesional Col1a2^creER; Rosa26^TdT+ fibroblast total density (c) and density within in inner core (d) or fibrotic border (e), with cKOs showing overall and inner fibroblast reduction with an intact but thinner lesional border (f), summarized via schematic (g), 14dpi. n = 6(control) or n = 5(cKO) slices/group (2 slices/mouse). h-i, ER-TR7 coverage (h) and lesion size (i, normalized per experiment) in control or cKO mice after tamoxifen pre-treatment only (tamoxifen days ⁻16–⁻14) without follow-up induction, 14dpi; n = 6(control) or n = 7(cKO) mice. j, S100A8⁺ neutrophils (PMN; left, surfaced; right, native) in controls (top) or cKOs (bottom), 14dpi (tamoxifen as in Fig. 4d). k, Time course showing cortical monocytes in controls/cKOs. n = 8(0dpi-control [non-littermate sham]), n = 6(2/4/7dpi-control, 2/7/21dpi-cKO), n = 12(14dpi-control), n = 9(21dpi-control), n = 3(0dpi-cKO), n = 5(4dpi-cKO), or n = 7(14dpi cKO) mice. l-q, Neutrophil or monocyte counts in meninges (l-m), blood (n-o), or 14dpi spinal cord (p-q) of controls/cKOs. n = 5(0dpi control [non-littermate sham], 7dpi cKO), n = 3(0dpi cKO), n = 6(2/4/7dpi control, 2/21dpi cKO), n = 12(14dpi control), n = 9(21dpi control), n = 5(l-m, 4dpi cKO), n = 6(n-o, 4dpi cKO), or n = 7(14dpi cKO) mice (l-o); n = 4 mice/group (p-q). r, Control/cKO spinal cords showing intact neurons without fibrosis/gliosis, 14dpi. s-t, Image (s) and quantification (t) of cCasp3⁺ puncta within corpus callosum in control or cKO mice, 14dpi. n = 4(sham-control), n = 6(sham-cKO), n = 8(stroke-control), or n = 7(stroke-cKO) mice (2–4 slices/mouse). u, Evans Blue extravasation in uninjured (resting or sham) or contralateral/lesioned hemispheres of controls/cKOs, 4dpi. n = 6(uninjured-control), n = 7(uninjured-cKO), or n = 9(contralateral/lesioned-control and cKO) mice. v, Quantification of overt bleeding in controls/cKOs, 4dpi. n = 9(control) or n = 7(cKO) mice. w, ER-TR7 coverage in control or cKO mice induced with late tamoxifen (beginning 14dpi), 28dpi. n = 6(control) or n = 7(cKO) mice. x, Co-expression of TGFβ-activating integrin pairs Itgav and Itgb1, Itgb6, or Itgb8 (snRNAseq). y-aa, Quantification of lesional Col1a1^GFP+ fibroblast total density (y) and density within in inner core (z) or fibrotic border (aa) in IgG- or ADWA11-treated mice, 14dpi. n = 3(IgG) or n = 4(ADWA11) mice (2 slices/mouse). ab-ae, Lesion size (ab, normalized per experiment), cortical monocytes (ac), and meningeal (ad) or blood neutrophils (ae) in IgG- and ADWA11-treated mice, 14dpi. n = 14(IgG) or n = 13(ADWA11) mice (ab, 2 slices/mouse); n = 7(IgG) or n = 8(ADWA11) mice (ac,ae); n = 6(IgG) or n = 7(ADWA11) mice (ad). af, Itgb8^TdT mouse, with perilesional/astrocytic TdT, 14dpi (insets: GFAP/TdT colocalization, yellow). ag, Lesion size in hGfap^cre; Itgb8^flox mice and controls (normalized per experiment), 14dpi. n = 12(control) or n = 7(cKO) mice (2 slices/mouse). ah-aj, Control or Emx1^cre; Itgb8^flox lesional images (ah), ER-TR7 coverage (ai), and lesion size (aj, normalized per experiment), 14dpi. n = 7 mice/group (2 slices/mouse). Two-way Student’s T-test (c-f,h,i,k [0dpi],p,q,v,w,y-ae,ag,ai,aj); two-way ANOVA, Sidak’s post-test (k [repeated measures, 7–21dpi, per timepoint; bold=lesioned-control/lesioned-cKO, grey=lesioned-control/contralateral-control, italics=lesioned-cKO/contralateral-cKO], t,u); multiple two-way T-tests, Holm-Sidak correction (l-o). 14μm slices; images represent two or more mice.

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