02423nas a2200517   4500000000100000000000100001008004100002260001500043653001000058653001800068653002100086653002800107653002500135653001700160653002800177653001900205653001100224653001100235653002600246653001600272653001400288653002500302653001500327653003600342653001600378653004200394100002700436700002500463700002000488700002100508700002400529700002400553700002200577700002200599700001500621700001600636700001900652700001700671700001700688700001900705245010900724300000900833490000700842520104200849022001401891       2020                            d  c2020-04-0610aAdult10aBRCA1 Protein10aBreast Neoplasms10aCell Culture Techniques10aCell Differentiation10aCell Lineage10aEpidermal Growth Factor10aErbB Receptors10aFemale10aHumans10aMammary Glands, Human10aMiddle Aged10aorganoids10aSingle-Cell Analysis10aStem cells10aTransforming Growth Factor beta10aYoung Adult10ap38 Mitogen-Activated Protein Kinases1 aJennifer M. Rosenbluth1 aRon C. J. Schackmann1 aG. Kenneth Gray1 aLaura M. Selfors1 aCarman Man-Chung Li1 aMackenzie Boedicker1 aHendrik J. Kuiken1 aAndrea Richardson1 aJane Brock1 aJudy Garber1 aDeborah Dillon1 aNorman Sachs1 aHans Clevers1 aJoan S. Brugge00aOrganoid cultures from normal and cancer-prone human breast tissues preserve complex epithelial lineages  a17110 v113 aRecently, 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.  a2041-1723