Extended Data Fig. 1: Reduced VEGFA signaling near Wnthigh progenitors in human CRC.
From: Apelin-driven endothelial cell migration sustains intestinal progenitor cells and tumor growth
(a) Wnthigh and Wntlow human CRC tumors are in CMS2 and CMS1, respectively. Distribution of CMS assignment for Wnthigh and Wntlow human CRC tumors, n = 469. (b) Angiogenic gene expression is decreased in CMS2 human CRC tumors compared to CMS1. Experimentally-derived angiogenesis signature score based on Masiero et al. 103 classified by CMS assignment, n = 2,275. p values from one-ANOVA with post-hoc Tukey test are listed. (c) VEGF-dependent angiogenesis gene expression103 is highest in Wntlow CRC tumors, n = 469 tumors. For boxplots, minimum (Q1) and maximum (Q3) of the box are the 25th and 75th percentile, the center is the median, the whiskers minima and maxima highlight the Q1-1.5xIQR and Q3 + 1.5xIQR, where IQR is the interquartile range (Q3-Q1). Points outside of these regions are outliers. (d-h) VEGFA signaling is compartmentalized into low Wnt signaling areas of human CRC tumors. Serial paraffin section immunostaining of high (H) or low (L) areas of PROX1 staining within the same Wnthigh CRC tumors for (d) PROX1, (e) PECAM1 and (f) ESM1. (g-h) Quantification of percentage (g) vessel area (left, p = 0.0401) or (h) ESM1+ vessels (left, p = 0.0008) in Wnthigh-Progenitor (Pro) or Wnthigh-Differentiated (Diff) areas or luminal/bulk or invasive (L/B or Inv) areas of Wntlow CRC tumors (n = 11 Wnthigh tumors and n = 8 Wntlow tumors). Scale bars: 100 μm. All data are shown as mean ± SD. *P < 0.05, ***P < 0.001, 2-tailed unpaired Student’s t-test.
