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. Author manuscript; available in PMC: 2022 Sep 7.
Published in final edited form as: Nat Med. 2021 Apr 15;27(4):640–646. doi: 10.1038/s41591-021-01295-9

Figure 2. Perivascular fibroblast marker proteins COL6A1 and SPP1 accumulate in enlarged perivascular spaces during ALS progression.

Figure 2

(A) Col6a1 and Spp1 mRNA specificity within CNS cell types. Bars represent relative count of RNA per cell ± SEM. (B) COL6A1 and SPP1 histochemistry in sALS and control spinal cords, bar: 10μm. (C) Quantifications of human tissue histochemistry from full frame 4x photos. sALS and Ctrl n=4 individuals (2-tailed t-test p-value). All boxplots show median, 2nd-3rd quartile and whiskers show +/-1.5 of the IQR. (D) Col6a1 and Spp1 accumulate around blood vessels (outlined with podocalyxin - cyan) in 14 week SOD1G93A mouse spinal cords. Immunofluorescence z-stack renderings of 16μm thick sections, bars: 100μm (overview), 10μm (insert). (E) Quantifications of immunofluorescence stainings in mice from full-frame 20x photos. SOD1G93A and BL/6 n=4, SOD1wt n=3 mice (2-tailed t-test p-value). (F) Increased perivascular spaces appear in presymptomatic (8 weeks) SOD1G93A mice spinal cords. Immunofluorescence for vascular (Col4a1) and astrocyte (Lama1) basement membranes, bar: 10μm. (G) Electron microscopy (tEM) of increased perivascular spaces in 14 week SOD1G93A mice. Astrocyte (red) and vascular (blue) basement membranes are indicated with lines. Perivascular space is indicated with asterisk, bar: 5μm. (H) COL6A1 and SPP1 accumulate within increased perivascular spaces (outlined with COL4A1) in spinal cords of sALS patients. 2 color histochemistry, bar: 10μm. (I) Quantifications of COL6A1 and SPP1 immunostainings from panel H. sALS and Ctrl n=4 individuals (two-tailed t-test p-value). (J) Quantifications of perivascular space increase in SOD1G93A mice from panel G (SOD1G93A and BL/6 n=4 mice) and in sALS patients from panel H (sALS and Ctrl n=4 individuals) (two-tailed t-test p-value). (K) Schematic representation of perivascular fibroblast activity and enlarged perivascular spaces in ALS.