Figure S1.
ITLN1 transcription is induced upon ER stress activation, and its absence or overexpression in intestinal epithelial cells does not affect colonic enteroendocrine cells, Tuft cells, and goblet cells. (A) Quantification of Hspa5 transcripts by qPCR in mouse small intestinal organoids in the presence or absence of tunicamycin (TM; n = 6). Symbols represent individual biological replicates. Bars represent arithmetic means. Data were compiled from two independent experiments. (B) Quantification of Hspa5 transcripts by qPCR in mouse small intestinal organoids after TM treatment alone or in the presence of 4μ8c, GSK2606414, or PF-429242 (n = 6–9). Symbols represent individual biological replicates. Bars represent arithmetic means. Data were compiled from two to three independent experiments. (C)ITLN1 transcripts after tunicamycin treatment alone (TM) or in the presence of 4μ8c, GSK2606414, or PF-429242 in Caco-2 cells (n = 9). Symbols represent biological replicate. Bars represent arithmetic means. Data were compiled from three independent experiments. (D)HSPA5 transcripts after tunicamycin treatment alone (TM) or in the presence of 4μ8c, GSK2606414, or PF-429242 in Caco-2 cells (n = 9). Symbols represent biological replicate. Bars represent arithmetic means. Data were compiled from three independent experiments. (E) Luciferase activity of ITLN1 promoter in HEK293 cells in relative luminescence units (RLU after transfection with XBP1s, XBP1u, or empty vector [control]; n = 4). Symbols represent biological replicate. Bars represent arithmetic means. Data were compiled from two independent experiments. (F) Quantification of enteroendocrine cells (Chromogranin A+ cells), Tuft cells (DCLK1+ cells), goblet cells (PAS+ cells) in the colon per crypt of Itln1−/− mice compared to wild-type littermates (wt; n = 8). wt = wild-type littermate from Itln1−/− colony. Symbols represent individual mice. (G) Quantification of enteroendocrine cells (Chromogranin A+ cells), Tuft cells (DCLK1+ cells), goblet cells (PAS+ cells) in the colon per crypt of TgVil-Itln1 mice compared to wild-type littermates (WT; n = 16). WT = wild-type littermate from TgVil1-Itln1 colony. Symbols represent individual mice. P values were calculated by unpaired T test (A, C, left panel, D, left panel, F, and G) or one-way ANOVA corrected for multiple comparisons with Dunnet (B, C, right panel, D right panel, and E). *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.

ITLN1 transcription is induced upon ER stress activation, and its absence or overexpression in intestinal epithelial cells does not affect colonic enteroendocrine cells, Tuft cells, and goblet cells. (A) Quantification of Hspa5 transcripts by qPCR in mouse small intestinal organoids in the presence or absence of tunicamycin (TM; n = 6). Symbols represent individual biological replicates. Bars represent arithmetic means. Data were compiled from two independent experiments. (B) Quantification of Hspa5 transcripts by qPCR in mouse small intestinal organoids after TM treatment alone or in the presence of 4μ8c, GSK2606414, or PF-429242 (n = 6–9). Symbols represent individual biological replicates. Bars represent arithmetic means. Data were compiled from two to three independent experiments. (C)ITLN1 transcripts after tunicamycin treatment alone (TM) or in the presence of 4μ8c, GSK2606414, or PF-429242 in Caco-2 cells (n = 9). Symbols represent biological replicate. Bars represent arithmetic means. Data were compiled from three independent experiments. (D)HSPA5 transcripts after tunicamycin treatment alone (TM) or in the presence of 4μ8c, GSK2606414, or PF-429242 in Caco-2 cells (n = 9). Symbols represent biological replicate. Bars represent arithmetic means. Data were compiled from three independent experiments. (E) Luciferase activity of ITLN1 promoter in HEK293 cells in relative luminescence units (RLU after transfection with XBP1s, XBP1u, or empty vector [control]; n = 4). Symbols represent biological replicate. Bars represent arithmetic means. Data were compiled from two independent experiments. (F) Quantification of enteroendocrine cells (Chromogranin A+ cells), Tuft cells (DCLK1+ cells), goblet cells (PAS+ cells) in the colon per crypt of Itln1−/− mice compared to wild-type littermates (wt; n = 8). wt = wild-type littermate from Itln1−/− colony. Symbols represent individual mice. (G) Quantification of enteroendocrine cells (Chromogranin A+ cells), Tuft cells (DCLK1+ cells), goblet cells (PAS+ cells) in the colon per crypt of TgVil-Itln1 mice compared to wild-type littermates (WT; n = 16). WT = wild-type littermate from TgVil1-Itln1 colony. Symbols represent individual mice. P values were calculated by unpaired T test (A, C, left panel, D, left panel, F, and G) or one-way ANOVA corrected for multiple comparisons with Dunnet (B, C, right panel, D right panel, and E). *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.

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