| First Author | Casey AE | Year | 2018 |
| Journal | J Cell Biol | Volume | 217 |
| Issue | 8 | Pages | 2951-2974 |
| PubMed ID | 29921600 | Mgi Jnum | J:264614 |
| Mgi Id | MGI:6194012 | Doi | 10.1083/jcb.201804042 |
| Citation | Casey AE, et al. (2018) Mammary molecular portraits reveal lineage-specific features and progenitor cell vulnerabilities. J Cell Biol 217(8):2951-2974 |
| abstractText | The mammary epithelium depends on specific lineages and their stem and progenitor function to accommodate hormone-triggered physiological demands in the adult female. Perturbations of these lineages underpin breast cancer risk, yet our understanding of normal mammary cell composition is incomplete. Here, we build a multimodal resource for the adult gland through comprehensive profiling of primary cell epigenomes, transcriptomes, and proteomes. We define systems-level relationships between chromatin-DNA-RNA-protein states, identify lineage-specific DNA methylation of transcription factor binding sites, and pinpoint proteins underlying progesterone responsiveness. Comparative proteomics of estrogen and progesterone receptor-positive and -negative cell populations, extensive target validation, and drug testing lead to discovery of stem and progenitor cell vulnerabilities. Top epigenetic drugs exert cytostatic effects; prevent adult mammary cell expansion, clonogenicity, and mammopoiesis; and deplete stem cell frequency. Select drugs also abrogate human breast progenitor cell activity in normal and high-risk patient samples. This integrative computational and functional study provides fundamental insight into mammary lineage and stem cell biology. |
