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  • Mammary molecular portraits reveal lineage-specific features and progenitor cell vulnerabilities.

Mammary molecular portraits reveal lineage-specific features and progenitor cell vulnerabilities.

The Journal of cell biology (2018-06-21)
Alison E Casey, Ankit Sinha, Rajat Singhania, Julie Livingstone, Paul Waterhouse, Pirashaanthy Tharmapalan, Jennifer Cruickshank, Mona Shehata, Erik Drysdale, Hui Fang, Hyeyeon Kim, Ruth Isserlin, Swneke Bailey, Tiago Medina, Genevieve Deblois, Yu-Jia Shiah, Dalia Barsyte-Lovejoy, Stefan Hofer, Gary Bader, Mathieu Lupien, Cheryl Arrowsmith, Stefan Knapp, Daniel De Carvalho, Hal Berman, Paul C Boutros, Thomas Kislinger, Rama Khokha
要旨

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.

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Sigma-Aldrich
ヒアルロニダーゼ from bovine testes, Type I-S, lyophilized powder, 400-1000 units/mg solid
Sigma-Aldrich
コラゲナーゼ Clostridium histolyticum由来, Type IA, 0.5-5.0 FALGPA units/mg solid, ≥125 CDU/mg solid, For general use
Sigma-Aldrich
α,α-Dicyanoethyl acetate, 98%