Fig. 3: Somatic SNV spectrum of mammary and tumor tissues with Brca1 deficiency revealed by scWES.
a The single cells and paired bulk tissues from different tumor developmental stages of Brca1+/+;MMTV-Cre;mT/mG and Brca1co/co;MMTV-Cre;mT/mG mice were sequenced. Wild-type mammary gland refers to the Brca1-wild-type mammary gland from 4-month-old mice with normal morphogenesis of mammary ductal tree. The premalignant mammary gland indicates the Brca1-deficient mammary gland with abnormal morphogenesis of mammary ductal tree. The arrows of the second panel indicate premalignant mammary gland hyperplastic foci. The arrows of the fourth panel indicate metastatic tumors buried in the liver. Scale bar, 3 mm. b Representative Brca1-WT and Brca1-MT mammary gland cells from Brca1-deficient mammary gland tissue. GFP (green) indicates Brca1-MT cells, Tomato (red) indicates Brca1-WT cells. Scale bar, 50 µm. c Representative Brca1-deficient primary breast tumor from Brca1co/co;MMTV-Cre;mT/mG mouse. GFP indicates Brca1-MT cells. Scale bar, 3 mm. d Representative H&E staining of the primary tumor from mouse 153 showing intratumor heterogeneity. Scale bar, 50 μm. e Quantification of exonic mutations according to the mutation type of Brca1-MT cells from different tumor developmental stages. VMMG, virgin mutant mammary gland cells (i.e., early stage of premalignant mammary gland cells from 4-month-old mouse); 476MMG, 476 mutant mammary gland cells (i.e., late stage of premalignant mammary gland cells from 11-month-old tumor-bearing mouse #476); 476PT, 476 primary tumor cells (i.e., malignant primary tumor cells from 11-month-old tumor-bearing mouse #476); 153PT, primary tumor cells (i.e., malignant primary tumor cells from 11-month-old tumor-bearing mouse #153); 153LMT, liver metastatic tumor cells (i.e., malignant metastatic tumor cells from 11-month-old tumor-bearing mouse #153). f Saturation curve of SNVs of single cells in each mouse.
