Fig. 1: In vivo mosaic partial reprogramming drives cell-autonomous and cell-non-autonomous epidermal dedifferentiation.

a Schematic of epidermal-specific OSKM inducible mouse models. Immunostaining for mCherry with GFP (b) or Sox2 (c) in the control and Epi-iOSKM skin (representative of 5 biological samples). Yellow arrows, mCherry⁺Sox2⁺ cells. d UMAP of scRNA-seq from IFE cells. Dashed lines, OSKM-enriched cell types. e Proportion of Basal I, II, Prolif I, II, and Supra I, II cells in IFE cells. Relative expression of Krt10 in IFE cells of each cell type (f), and in Supra IFE cells of each condition (g). Two-tailed Mann-Whitney U test with Bonferroni correction. h Krt10 and mCherry staining in the control and Epi-iOSKM skin with quantifications of Krt10⁻ cells in the suprabasal epidermis. Yellow and gray arrowhead, Krt10⁻ cells in the suprabasal epidermis with and without mCherry expression, respectively. n = 6 from 3 mice/condition. i UMAP with pseudotime and trajectory inference (top) and pseudotime in Supra IFE cells (bottom). Two-tailed Mann-Whitney U test with Benjamini-Hochberg correction. j Proportion of Prolif, Supra, and Basal cells. k Ki67 and mCherry staining in control and Epi-iOSKM skin with quantifications of Ki67⁺ cells. n = 9 from 3 mice/condition. l–n PAGA graphs showing velocity results in IFE cells. Blue, red, and black arrows illustrate transition patterns from Basal toward Supra cells, from Supra toward Basal/Prolif cells, and others, respectively (l). Bold dashed black arrows illustrate transition patterns from Krt10-low cells to Krt10-high cells (m) and Ki67-high cells to Ki67-low cells (n), while bold black arrows illustrate the reverse transition patterns. Gray and yellow arrows illustrate others (m, n). o Cell-autonomous and non-autonomous effects of mosaic partial epidermal reprogramming. Data are presented as mean ± SEM (one-way ANOVA with Tukey’s and Dunnett’s T3 multiple comparisons test in h, k). Box plots show the median, interquartile range, and 1.5-fold interquartile range whiskers alongside individual outliers in (f, g, i). White dashed lines, the boundary between the epidermis and dermis in (b, c, h, k). Pink arrows, mCh^neg-enriched cell types (d, e). Scale bars, 50 µm (b, c, h, k).