Extended Data Fig. 10: Stress drives CRC growth via GABRE.
(a-d) CRS-induced neural/immune changes in male C57BL/6 J mice: increased ChAT+ cells in muscular layer (a, n = 5, 6 mice for Control and CRS respectively), elevated Ly6C+ cells in mucosa (b, n = 5, 6 mice for Control and CRS respectively), unchanged ChAT+ cells (c, n = 10, 5 mice for Control and CRS respectively) and Ly6C+ cells (d, n = 7, 5 mice for Control and CRS respectively) in rectal tumors. (e-k) CRS in male C57BL/6 J CDX model with the injection of Gabre knockdown CMT93 cells. Control cells-formed tumors: morphology (f), weight (g), volume (h), n = 8, 6 mice for Control and CRS respectively. Gabre-knockdown cells-formed tumors: morphology (i), weight (j), volume (k), n = 8, 3 mice for Control and CRS respectively. (l-q) CRS-induced neural/immune changes in female C57BL/6 J mice: increased LS c-Fos+ neurons (l, n = 3 mice per group), elevated serum corticosterone (m, n = 8 mice per group) and colorectal GABA (n, n = 8 mice per group), decreased colorectal Ach (o, n = 8 mice per group), increased ChAT+ cells in muscular layer (p, n = 7 mice per group) and unchanged Ly6C+ cells in mucosa (q, n = 8 mice per group). (r-u) Chemogenetic inhibition of LSGABA neurons in female CDX model suffering from CRS (r). Tumor morphology (s), weight (t), volume (u). n = 5, 4, 4, 6 mice for Control+Control, Control+CRS, hM4Di+Control, hM4Di+CRS respectively. Data are presented as mean ± SEM. Two-tailed unpaired student’s t test (a-b, d, g-h, j-l, o-q), two-tailed unpaired student’s t test with Welch’s correction (c), two-tailed Mann Whitney test (m), two-tailed Kolmogorov-Smirnov test (n) and Ordinary one-way ANOVA with Tukey’s multiple comparisons test (t-u) are used. n.s., not significant.
