Extended Data Fig. 8: Validation of perturbed-state atlas.
a–o, UMAP representations of the distribution of fibroblasts across tissues and perturbations. p–u, Heat maps showing average relative gene expression in Pi16+, Col15a1+, Adamdec1+, Cxcl5+, and Lrrc15+ clusters (z-scored per row) in the following categories. p, Cytokines and chemokines. q, Wnt-associated genes. r, ECM-associated genes. s, Collagens and laminins. t, Matrix metalloproteases and cathepsins. u, Receptors and surface molecules. v, Expression of pathway-responsive genes in perturbed-state atlas clusters as assessed by PROGEN(y) analysis (z-scored per row). w, RNAscope for Dpt (blue) and Grem1 (red) in non-lesional colon (top) and lesional colon (bottom) on day 7 after induction of DSS colitis. Data are representative of three experiments. Scale bars, 50 μm (top) and 250 μm (bottom). x, Ly6a and Cd34 expression in perturbed-state clusters. Wilcoxon’s rank sum test, P < 0.05. y, Pseudotime(s) visualized using principal curves representing trajectories of fibroblast differentiation across perturbed-state fibroblast object. Blue lines show trajectory to activated clusters, grey lines show trajectory to clusters with a steady-state analogue. Pi16+ cluster set as root. z, Representative FACS strategy for subcutaneous tumour experiments. a′, Representative flow cytometry plots showing frequency of YFP+ cells in LRRC15+ fibroblasts from KPR3070 subcutaneous tumour at day 21 post-inoculation in DptIRESCreERT2wt/wtRosa26LSLYFPwt/loxP animals. b′, Quantification of FACS data (Fig. 3d, Extended Data Fig. 8z, a′). Data are from b′ or representative of 2 (z–a′) or 3 (w) experiments. Each dot represents one mouse (b′). n = 2 (b′) or representative of 2 (z–a′) or 3 (w) biologically independent experiments.
