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. Author manuscript; available in PMC: 2021 Jan 12.
Published in final edited form as: Nature. 2019 Jan 16;565(7740):505–510. doi: 10.1038/s41586-018-0858-8

Figure 4. Identification of Dll4-Notch3 as driver for diabetic vascular basement membrane thickening.

Figure 4

a, Representative images of Col IV in diabetic blood vessel organoids (NC8), treated with antibodies against Jagged-1, Notch1, Notch3, or recombinant Dll1 and Dll4. The thickness of the Col IV+ coat of vessels was measured in optical cross-sections. Non-diabetic n=132, Vehicle n=139, α-Jagged1 n=141, Dll1 n=132, Dll4 n=153, α-Notch1 n=156, α-Notch3 n=156 lumina were analysed from 3 independent biological replicates with equal sample size. Mean ± SD. *** p<0.0001 (One-way ANOVA). b, Dermal blood vessels of T2D patients (diabetic) and healthy controls (non-diabetic) were stained for Notch3 and SMA. c, Hes5 and SMA were co-stained in dermal sections of T2D patients (diabetic) and non-diabetic controls. Note the strong Hes5 signal in pericytes (SMA) of diabetic patients. d,e, Quantification of Notch3 and Hes5 expression data from c and d. Mean ± S.E.M of n = (non-diabetic =4, diabetic=4) independent patients. * p=0.043 two-tailed student t-test. Scale bars a=50μm, b,c=20μm.