Fig. 4: HIF1α mediates the transition to proto-myofibroblasts and tissue contraction.
a, HIF1α activity versus expression correlations in the different fibroblast clusters from the scRNA-seq data. Pearson’s R coefficient is shown. b, Representative micrographs of wounds in Cd201creERR26Ai14 and PdpncreERR26mTmG mice, and fascia explant at indicated timepoints after injury or culture showing the expression of HIF1α. c, Representative high-magnification images of control and HIF1α inhibitor-treated PdpncreERR26mTmG wounds showing the expression of pSTAT3 or RUNX2 in GFP-traced cells (left) and marker-expressing cell ratios (right). n = 6 wounds from 3 biological replicates. d, Representative photographs of control, fascia or proinflammatory HIF1α null wounds at 9 dpi (left). Wound area quantification over time (middle), and contraction at 7 dpi (top right) and at 9 dpi (bottom right). Colours of the image outlines indicate treatments in the graph. n = 6 wounds from 3 biological replicates for each genotype. e, Masson’s trichrome staining (top) and wound maturation-related measurements (bottom) of 9 dpi wounds from indicated genotypes. n = 12 images from 3 biological replicates per each genotype. f,g, Fascia ECM fate mapping in 3 dpi wounds treated with HIF1α inhibitor. f, Representative low-magnification (left) and high-magnification (right) images of control or HIF1α inhibitor-treated wounds. g, Lacunarity and fractal dimension density plots to assess porosity (lacunarity) and shape complexity (fractal dimension) differences in labelled ECM from control or HIF1α inhibitor-treated wounds (left) and individual comparisons (right). n = 11 images from 3 biological replicates for each condition. The dotted line delimits the wound region. Arrowheads indicate the original injury site. All P values (except in a) were obtained from two-tailed t-tests. Scale bars: 500 μm (e and f, left) and 50 μm (b,c, and f, right).
