Figure 5 from β-Catenin Drives Butyrophilin-like Molecule Loss and γδ T-cell Exclusion in Colon Cancer
Year: 2023
Type: other
Abstract: HNF4A and HNF4G regulate butyrophilin-like molecule expression in normal gut tissue. A, Schematic of mouse and human promoter regions of indicated genes. Putative HNF4A/G-binding sites are shown in green; CDX1 and CDX2 binding sites are shown in orange. B, Images of CDX1, CDX2, HNF4A and HNF4G protein expressions in SI of WT mice (n = 4); scale bar, 500 μm. C, Integrative Genomics Viewer analysis of HNF4A/HNF4G ChIP-seq data at mouse Btnl gene loci. D, Fold change in expression levels of indicated genes in WT organoids transduced with shRNA constructs targeting Hnf4 g transcripts. Each dot represents one organoid from one mouse (n = 4). Data are presented as mean ± SD. E, Butyrophilin-like molecule expression determined by RNA-seq analysis of SI in indicated mouse models. Each dot represents one mouse (n = 3). Data are presented as mean ± SD. F, Images of organoids from WT mice treated with DMSO control or HNF4A/G inhibitor (HNF4i) representative of 3/group. Fold change in expression levels of indicated genes. Each dot represents one organoid from one mouse (n = 3). Data are presented as mean ± SD. G, Correlation between HNF4G expression as determined by TempO-seq and γδ T-cell density determined by IHC in the Scotland cohort. Units on axes are normalized counts x 103. Each dot represents one tumor (n = 77). P and r values determined by Pearson correlation. H, Correlation between BTNL3 or BTNL8 expression and HNF4G expression units on axes are normalized counts x 103. Each dot represents one tumor (n = 82 Scotland cohort, 258 Marisa cohort). P and r values determined by Pearson correlation. *, P < 0.05; **, P < 0.01; ***, P < 0.001 (unpaired t test or one-way ANOVA followed by Tukey post hoc test).
Authors: Toshiyasu Suzuki, Anna Kilbey, Nuria Casa-Rodríguez, Amy Lawlor, Anastasia Georgakopoulou, Hannah Hayman, Kyi Lai Yin Swe, Anna Nordin, Claudio Cantù, Pierre Vantourout, Rachel A. Ridgway, Ryan M. Byrne, Lei Chen, Michael P. Verzi, David M. Gay, Ester Gil Vázquez, Hayley L. Belnoue-Davis, Kathryn Gilroy, Anne Helene Køstner, Christian Kersten, Chanitra Thuwajit, Ditte K. Andersen, Robert Wiesheu, Anett Jandke, Karen Blyth, Antonia K. Roseweir, Simon J. Leedham, Philip D. Dunne, Joanne Edwards, Adrian Hayday, Owen J. Sansom, Seth B. Coffelt
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4385549489