Fig. 1: Tumors induce Notch1 overactivation in the adipose tissue endothelium.

a, Timeline of AT-EC isolation from precachectic mice injected intraperitoneally (i.p.) with KPC pancreatic adenocarcinoma cells. b, Relative mass of sWAT collected from KPC precachectic mice (n = 6 animals per group). c, Top ten IPA-predicted upstream regulators of transcriptomic changes in sWAT AT-ECs from precachectic versus non-tumor-bearing mice. Plotted are z scores and –log₁₀ (P values); n = 3–4. d, mRNA levels of prototypical Notch target genes and signaling components in precachectic AT-ECs (n = 6 animals per group). e, Representative images of ERG (DAB, brown) and Notch1 (AP, red) co-stainings comparing sWAT from PBS-injected (control) and KPC-injected mice; scale bar, 50 µm. f, Quantification of ERG⁺Notch1⁺ ECs in sWAT (n = 6 animals per group, ten images averaged per mouse); AU, arbitrary units. g, Enrichment of an ‘AT-EC Notch1 gene signature’ was analyzed in publicly available datasets from whole vWAT biopsies from healthy individuals and individuals with precachexia and cachexia (GSE131835). h, Enrichment plots of the ‘AT-EC Notch1 gene signature’ comparing precachectic and cachectic vWAT to healthy vWAT; NES, normalized enrichment score; FDR, false discovery rate. Data shown represent mean ± s.e.m. Data were analyzed by unpaired, two-sided t-test with Welch correction. Experiments in b and d were performed twice with consistent results. Results shown are from one representative experiment.

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