Fig 2: Effects of exosomes derived from fisetin-treated keratinocytes on hair follicle stem cells (HFSCs). (A) Localization of β-catenin in HFSCs was evaluated by immunocytochemistry using anti-β-catenin antibody. Nuclear localization of β-catenin (red in pie chart) in HFSCs treated with exosomes was quantitatively determined using IN Cell Analyzer 2200. (B) Expression of axin in HFSCs treated with exosomes was quantitatively determined using qRT-PCR. (C) Ki67+ cells in HFSCs were detected by immunocytochemistry using anti-Ki67 antibody. The number of Ki67+ cells (red in pie chart) was determined using IN Cell Analyzer 2200. Statistical significance was determined using a two-sided Student’s t-test. Statistical significance was defined as p < 0.05 (* p < 0.05).

Fig 3: BRAFV600E induction results in differential expression of cell cycle and senescence markers in ATII cells from uninduced, induced non-tumor alveolar parenchyma and lung adenomas.Representative images (from the left) and quantifications (right) showing SPC+ cells staining positive for A Ki67, B pRb, C γH2AX, D p21CIP1, E p53 and F pSTAT3 double immunostainings in normal alveolar epithelium of control mice (left), non-tumor areas (center) and adenomas (right) from lung sections of BRAFV600E mice. Quantifications were performed on four to ten different random areas of at least four hyperplastic nodules sections and four to ten different random areas of uninduced alveolar parenchyma. Data are expressed as mean ± SEM; n represents respectively the number of animals per group in “alveoli” samples and the number of adenomas in the “tumor” samples. For each condition at least 4 mice were used. The percentages shown in the charts were obtained dividing the number of double positive cells by the overall number of SPC + cells. *P < 0.05; **P < 0.01; ***P < 0.001, ns = not significant. (ANOVA test with Tukey’s post-hoc correction). Arrows point to selected positive cells for the indicated marker.

Fig 4: Dectin‐3−/− mice have increased tumor load upon AOM‐DSS treatment than WT miceSingle‐housed WT mice and Dectin‐3−/− mice (n = 8 for each group) were injected intraperitoneally with one dose of AOM (10 mg/kg), followed by three cycles of feeding water with 2% DSS. After induction of tumorigenesis, mice were euthanized on day 100. ARepresentative images of colon tumors were shown. Scale bars, 10 mm.BTumor number, tumor size, and tumor load in each mouse were measured.C, DHistological analysis of colon tumors was shown by hematoxylin and eosin (HE) staining. Tumors were microscopically analyzed and classified as low or high grade. Histological score was assessed by a pathologist. Scale bars, 25 µm.E, FTumor tissues were stained for Ki67 and p‐STAT3. The percentage of Ki67‐positive and p‐STAT3‐positive cells was quantified. Scale bars, 25 µm.GProportion of CD11b+F4/80+ and RORγt+/CD45+lin− cells was analyzed in colonic LP cells and mLNs among tumor‐bearing WT and Dectin‐3−/− mice by flow cytometry.HRelative expression of Il‐6, Il‐22, Cxcl1, and Il‐17a in LP cells from tumor‐bearing WT and Dectin‐3−/− mice were detected using qPCR. Data information: Data with error bars are represented as mean ± SD. Each panel is a representative experiment of at least three independent biological replicates. *P < 0.05, **P < 0.01, ***P < 0.001 as determined by unpaired Student’s t‐test. See also Fig EV1.

Fig 5: Systemic PHGDH depletion is non-toxic. a Overall survival of mice expressing shPHGDH (N = 23) or the control shRenilla (shREN, N = 26). b Weight of male and female mice expressing shPHGDH (male, N = 16; female, N = 15) or shREN (male, N = 13; female, N = 10). Mice were placed on doxycycline at weaning. c Representative hematoxylin and eosin stained (N = 10+) and Ki-67 immunostained (N = 5 each) large intestine sections from shPHGDH and shREN mice at endpoint. d Representative hematoxylin and eosin stained bone marrow sections from shPHGDH and shREN mice (N = 10+) at endpoint. e Red blood cell counts of shREN (N = 31) and shPHGDH (N = 33) mice at 8 months. f White blood cell counts of shREN (N = 31) and shPHGDH (N = 33) mice at 8 months. g Oral glucose tolerance test at 100 days on doxycycline. Male and female shPHGDH and shREN mice were challenged with 2 g/kg glucose at time = 0, and blood glucose levels were assayed at the indicated time points. Male shPHGDH (N = 7), male shREN (N = 7), female shPHGDH (N = 6), female shREN (N = 10)