Abstract

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.

Organoid technology has enabled the generation of several breast cancer organoids. Here, the authors combine propagation of normal human mammary tissues with mass cytometry to evaluate the ability of organoid culture technologies to preserve stem cells and differentiated cell types.

Details

Title
Organoid cultures from normal and cancer-prone human breast tissues preserve complex epithelial lineages
Author
Rosenbluth, Jennifer M 1   VIAFID ORCID Logo  ; Schackmann Ron C J 1 ; Kenneth, Gray G 1 ; Selfors, Laura M 1   VIAFID ORCID Logo  ; Li Carman Man-Chung 1   VIAFID ORCID Logo  ; Mackenzie, Boedicker 1 ; Kuiken, Hendrik J 1 ; Richardson, Andrea 2 ; Brock, Jane 2 ; Garber, Judy 3 ; Dillon, Deborah 2 ; Sachs, Norman 4   VIAFID ORCID Logo  ; Clevers Hans 4   VIAFID ORCID Logo  ; Brugge, Joan S 1 

 Harvard Medical School, Department of Cell Biology, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
 Brigham & Women’s Hospital, Department of Pathology, Boston, USA (GRID:grid.62560.37) (ISNI:0000 0004 0378 8294) 
 Dana-Farber Cancer Institute, Department of Medical Oncology, Boston, USA (GRID:grid.65499.37) (ISNI:0000 0001 2106 9910) 
 Hubrecht Institute, Utrecht, The Netherlands (GRID:grid.419927.0) (ISNI:0000 0000 9471 3191) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2386865051
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.