TY - JOUR KW - Adult KW - BRCA1 Protein KW - Breast Neoplasms KW - Cell Culture Techniques KW - Cell Differentiation KW - Cell Lineage KW - Epidermal Growth Factor KW - ErbB Receptors KW - Female KW - Humans KW - Mammary Glands, Human KW - Middle Aged KW - organoids KW - Single-Cell Analysis KW - Stem cells KW - Transforming Growth Factor beta KW - Young Adult KW - p38 Mitogen-Activated Protein Kinases AU - Jennifer M. Rosenbluth AU - Ron C. J. Schackmann AU - G. Kenneth Gray AU - Laura M. Selfors AU - Carman Man-Chung Li AU - Mackenzie Boedicker AU - Hendrik J. Kuiken AU - Andrea Richardson AU - Jane Brock AU - Judy Garber AU - Deborah Dillon AU - Norman Sachs AU - Hans Clevers AU - Joan S. Brugge AB - Recently, organoid technology has been used to generate a large repository of breast cancer organoids. Here we present an extensive evaluation of the ability of organoid culture technology to preserve complex stem/progenitor and differentiated cell types via long-term propagation of normal human mammary tissues. Basal/stem and luminal progenitor cells can differentiate in culture to generate mature basal and luminal cell types, including ER+ cells that have been challenging to maintain in culture. Cells associated with increased cancer risk can also be propagated. Single-cell analyses of matched organoid cultures and native tissues by mass cytometry for 38 markers provide a higher resolution representation of the multiple mammary epithelial cell types in the organoids, and demonstrate that protein expression patterns of the tissue of origin can be preserved in culture. These studies indicate that organoid cultures provide a valuable platform for studies of mammary differentiation, transformation, and breast cancer risk. BT - Nature Communications DA - 2020-04-06 DO - 10.1038/s41467-020-15548-7 IS - 1 LA - eng N2 - Recently, organoid technology has been used to generate a large repository of breast cancer organoids. Here we present an extensive evaluation of the ability of organoid culture technology to preserve complex stem/progenitor and differentiated cell types via long-term propagation of normal human mammary tissues. Basal/stem and luminal progenitor cells can differentiate in culture to generate mature basal and luminal cell types, including ER+ cells that have been challenging to maintain in culture. Cells associated with increased cancer risk can also be propagated. Single-cell analyses of matched organoid cultures and native tissues by mass cytometry for 38 markers provide a higher resolution representation of the multiple mammary epithelial cell types in the organoids, and demonstrate that protein expression patterns of the tissue of origin can be preserved in culture. These studies indicate that organoid cultures provide a valuable platform for studies of mammary differentiation, transformation, and breast cancer risk. PY - 2020 EP - 1711 T2 - Nature Communications TI - Organoid cultures from normal and cancer-prone human breast tissues preserve complex epithelial lineages VL - 11 SN - 2041-1723 ER -