Fig. 2: Injury-responsive-like conversion in transiently OSKM-expressing and their neighboring cells.
a Heatmap of the gene module scores (associated with gene sets upregulated in the epidermis of Epi-iOSKM mice) in IFE cells of each condition. Pink boxes, cell-non-autonomous effects. b, c scRNA-seq data from IFE cells of control and Epi-iOSKM mice in our study and reference data from unwounded and wounded IFE cells were integrated. UMAP with unbiased clustering (b), and proportion of each cluster in reference (c, top) and our study (c, bottom). Red boxes, clusters enriched in wounded, mChneg, and mChpos IFE cells (c). UMAP of IFE cells from reference (d, left) and our study (d, right) with annotated cell types, and proportion of each cell type in cluster 6 (e). f UMAP with relative expression of Krt17 (top) and Krt6a (bottom). g Relative expression of Krt17 (top) and Krt6a (bottom) in IFE cells of each condition. Immunostaining for mCherry with Krt17 (h) or Krt6a (i) with MFI quantification in control and Epi-iOSKM epidermis. Data are mean ± SEM (n = 6 from 3 mice/condition, one-way ANOVA with Tukey’s multiple comparisons test). Module score of genes associated with cellular response to hypoxia (j) or cytokine signaling in immune system (k) by REACTOME. Box plots show the median, interquartile range, and 1.5-fold IQR whiskers with outliers (n = 3013 from 3 mice (control), 1612 (mChneg) or 2101 (mChpos) from 6 mice). Immunostaining of HIF-1α (l), phospho-STAT3 (m) and mCherry in skin from control and Epi-iOSKM mice (representative of 3 biological samples). n Diagram illustrating partial epidermal reprogramming conferring healing features and cellular plasticity within epidermal lineages compared to full reprogramming. Bold dashed lines, cluster 6 in integrated UMAP (b, d, f). White dashed lines, boundary between the epidermis and dermis (h, i, l, m). Pink arrows, the cell non-autonomous effects of partial epidermal reprogramming (h, i, l, m). Asterisks, autofluorescence in the skin (l, m). Two-tailed Mann–Whitney U test with Bonferroni correction (g, j, k). Scale bars, 50 µm (h, i, l, m). iPSCs, induced pluripotent stem cells; HF hair follicle, MFI mean fluorescence intensity.
