Extended Data Fig. 8: HIF1α instructs the transition into (proto)myofibroblasts.

a. Control (top) or HIF1α inhibitor-treated (bottom) explants after 6 days of culture (left), area over time (middle), and contraction (right) measurements. N = 6 (control) and 3 (inhibitor) replicates. b. Immunolabeling (left) and marker-positive cell ratios (right) of proinflammatory fibroblast (PDPN⁺) or myofibroblasts (αSMA⁺) in control (top) or inhibitor-treated (bottom) explants. N = 3 biological replicates. c. Immunolabeling (top left) and YAP1⁺ cell ratios (bottom left) upon chemical TAZ agonism. N = 3 (controls) and 4 (agonist) biological replicates. TAZ agonist-treated (centre top) and combined treatments with the inhibitor (centre middle) or RA (centre bottom) explants after 6 days of culture. Area over time (top right), and contraction (bottom right) measurements. N = 3 biological replicates. d. TGFβ1-treated (top left) and combined treatments with the inhibitor (centre left) or RA (bottom left) explants after 6 days of culture. Area over time (top right), and contraction (bottom right) measurements. N = 3 biological replicates. e. Immunolabeling (top) and pSMAD2⁺ cell ratios (bottom). N = 3 biological replicates. f. Correlation of HIF1α regulon vs hypoxia activity, positively regulated genes involved in TGFβ pathway (bottom). g-h. UMAPs of gene expression and schematic representation of HIF1α-regulated TGFβ modulators. i. Representative photographs (left) of control (top) or inhibitor-treated wounds (bottom) at 7 dpi. Wound area measurements over time (top right) and overall contraction at 7 dpi (bottom right). N = 3 biological replicates. j. Trichrome-stained micrographs of control (top) and treated wounds (bottom) at 7 dpi. k. Micrographs of control (top left) and treated 3 dpi wounds (bottom left) immunolabeled for CD45/PTPRC and positive cell ratios (right). N = 6 (control) and 5 (treated) wounds from 3 biological replicates. All p-values from two-tailed T-tests. Scale bars: 2 mm in explants photographs (a, c-d), 500 microns (g), and 50 microns (b-c, e, and h).