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Publication : Embryonic Barcoding of Equipotent Mammary Progenitors Functionally Identifies Breast Cancer Drivers.

First Author  Ying Z Year  2020
Journal  Cell Stem Cell Volume  26
Issue  3 Pages  403-419.e4
PubMed ID  32059806 Mgi Jnum  J:306052
Mgi Id  MGI:6710435 Doi  10.1016/j.stem.2020.01.009
Citation  Ying Z, et al. (2020) Embryonic Barcoding of Equipotent Mammary Progenitors Functionally Identifies Breast Cancer Drivers. Cell Stem Cell 26(3):403-419.e4
abstractText  Identification of clinically relevant drivers of breast cancers in intact mammary epithelium is critical for understanding tumorigenesis yet has proven challenging. Here, we show that intra-amniotic lentiviral injection can efficiently transduce progenitor cells of the adult mammary gland and use that as a platform to functionally screen over 500 genetic lesions for functional roles in tumor formation. Targeted progenitors establish long-term clones of both luminal and myoepithelial lineages in adult animals, and via lineage tracing with stable barcodes, we found that each mouse mammary gland is generated from a defined number of approximately 120 early progenitor cells that expand uniformly with equal growth potential. We then designed an in vivo screen to test genetic interactions in breast cancer and identified candidates that drove not only tumor formation but also molecular subtypes. Thus, this methodology enables rapid and high-throughput cancer driver discovery in mammary epithelium.
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