Extended Data Fig. 1: Injury induces tumors only in HrasG12V/+-max models.
From: Injury prevents Ras mutant cell expansion in mosaic skin
a) Skin tissue architecture cartoon schematic. b, c, d) H&E staining of uninjured and injured ear skin within 2 weeks PWI with magnified insets. n = 5 wild-type, n = 5 HrasG12V/+-max and n = 4 HrasG12V/+-mosaic. b) Wild-type tissue exhibits normal histology (left) and injured tissues (right) demonstrates mixed inflammatory infiltrate and increased fibroblast number consistent with early scar tissue. c) HrasG12V/+-mosaic uninjured tissue (left) shows normal histology. Injured ear (right) exhibits dermal fibrosis consistent with normal scar tissue. d) HrasG12V/+-max uninjured tissue (left) with normal epithelial thickness and differentiation with mild orthokeratotic hyperkeratosis (stratum corneum thickening with normal basket-weave appearance). In the HrasG12V/+-max injured ear (right) adjacent to the wound there is notable acanthosis and hypergranulosis of the epithelium with compact orthokeratotic hyperkeratosis. Cytologic atypia is present. e) Aberrant growth in the injured-HrasG12V/+-max model in contrast to the normal epithelium in the injured-HrasG12V/+-mosaic model (day-14 PWI). f) (right) Heat maps of epithelial thickness in the top-down (x-y) view of representative two-photon images adjacent to injury in the back skin of HrasG12V/+-mosaic and HrasG12V/+-max identifying aberrant growth. Scale bar, 100 μm. (left) Quantification of average epithelial thickness 14 days PWI at different distances from wound edge in HrasG12V/+-mosaic and HrasG12V/+-max. n = 3 mice (mean±s.d.). g, h) H&E staining of injured back skin within two weeks PWI. n = 3 mice. g) HrasG12V/+-mosaic injured back shows skin dermal fibrosis with vertically oriented blood vessels consistent with scar. The overlying epidermis is normal thickness with orthokeratosis. h) HrasG12V/+-max injured back skin with dermal scar and the overlying epidermis is characterized by hyperkeratosis and papillomatosis. i) Aberrant growth around the wound of the HrasG12V/+-max model in contrast to the normal epithelium of the HrasG12V/+-mosaic model.
