Extended Data Fig. 1: Extended phenotypic characterization of Dnmt3a loss impacting atherosclerosis.
a-b, Bi-allelic loss of Dnmt3a in hematopoietic cells accelerates atherosclerosis. (a) Oil red O (ORO) stained aortic root sections in female Ldlr−/− mice transplanted with either Dnmt3a+/+; Vav1-Cre (WT) or Dnmt3a−/−; Vav1-Cre (KO) marrow, in a 1:9 ratio with WT, after 9 weeks of feeding on high-fat, high-cholesterol diet. Atheromata are demarcated by dashed lines. Scale bars = 200 µm. (b) Quantification of lesion area in the aortic root. N = 10 animals for both groups. Unpaired two-tailed t-test with Welsh’s correction. Box plot shows min, 25th percentile, median, 75th percentile and max. c, Single-allele loss of Dnmt3a has minimal impact on atherosclerosis. Shown is lesion area after 9 weeks on diet in female Ldlr−/− mice that were transplanted with either Dnmt3a + /−; Vav1-Cre marrow (left) or Dnmt3a + /−; Lyz2-Cre marrow (right), compared to WT controls. N = 10 animals per group for Vav1-Cre experiment, N = 15 per group for Lyz2-cre experiment. Unpaired two-tailed t-test with Welsh’s correction. Box plots show min, 25th percentile, median, 75th percentile and max. d-e, Lesion size in advanced atherosclerosis does not differ between WT and Dnmt3a knock-out. (d) ORO-stained aortic root sections in female Ldlr−/− mice transplanted with either Dnmt3a+/+; Vav1-Cre (WT) or Dnmt3a−/−; Vav1-Cre (KO) marrow, after 20 weeks of feeding on high-fat, high-cholesterol diet. Atheromata are demarked by dashed lines. Scale bars = 200 µm. (e) Quantification of lesional area in the aortic root. N = 4 mice for WT and N = 5 for KO group. Unpaired two-tailed t-test with Welsh’s correction. Box plot shows min, 25th percentile, median, 75th percentile and max. f, Isotype control (rabbit IgG) IHC staining for CD68 on aortic root with atheroma (control for Fig. 1c-d) demonstrates specificity of staining. Scale bar = 100 µm.
