Organoid cultures from normal and cancer-prone human breast tissues preserve complex epithelial lineages

Jennifer M Rosenbluth; Ron C J Schackmann; G Kenneth Gray; Laura M Selfors; Carman Man-Chung Li; Mackenzie Boedicker; Hendrik J Kuiken; Andrea Richardson; Jane Brock; Judy Garber; Deborah Dillon; Norman Sachs; Hans Clevers; Joan S Brugge

doi:10.1038/s41467-020-15548-7

Organoid cultures from normal and cancer-prone human breast tissues preserve complex epithelial lineages

Jennifer M Rosenbluth, Ron C J Schackmann, G Kenneth Gray, Laura M Selfors, Carman Man-Chung Li, Mackenzie Boedicker, Hendrik J Kuiken, Andrea Richardson, Jane Brock, Judy Garber, Deborah Dillon, Norman Sachs, Hans Clevers, Joan S Brugge

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

127 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1711
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-15548-7
Publication status	Published - 06 Apr 2020

Access to Document

10.1038/s41467-020-15548-7

Cite this

Rosenbluth, J. M., Schackmann, R. C. J., Gray, G. K., Selfors, L. M., Li, C. M.-C., Boedicker, M., Kuiken, H. J., Richardson, A., Brock, J., Garber, J., Dillon, D., Sachs, N., Clevers, H., & Brugge, J. S. (2020). Organoid cultures from normal and cancer-prone human breast tissues preserve complex epithelial lineages. Nature Communications, 11(1), 1711. https://doi.org/10.1038/s41467-020-15548-7

@article{dbb2b2c478554781b9d117137c8e7dae,

title = "Organoid cultures from normal and cancer-prone human breast tissues preserve complex epithelial lineages",

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.",

author = "Rosenbluth, {Jennifer M} and Schackmann, {Ron C J} and Gray, {G Kenneth} and Selfors, {Laura M} and Li, {Carman Man-Chung} and Mackenzie Boedicker and Kuiken, {Hendrik J} and Andrea Richardson and Jane Brock and Judy Garber and Deborah Dillon and Norman Sachs and Hans Clevers and Brugge, {Joan S}",

year = "2020",

month = apr,

day = "6",

doi = "10.1038/s41467-020-15548-7",

language = "English",

volume = "11",

pages = "1711",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

Rosenbluth, JM, Schackmann, RCJ, Gray, GK, Selfors, LM, Li, CM-C, Boedicker, M, Kuiken, HJ, Richardson, A, Brock, J, Garber, J, Dillon, D, Sachs, N, Clevers, H & Brugge, JS 2020, 'Organoid cultures from normal and cancer-prone human breast tissues preserve complex epithelial lineages', Nature Communications, vol. 11, no. 1, pp. 1711. https://doi.org/10.1038/s41467-020-15548-7

TY - JOUR

T1 - Organoid cultures from normal and cancer-prone human breast tissues preserve complex epithelial lineages

AU - Rosenbluth, Jennifer M

AU - Schackmann, Ron C J

AU - Gray, G Kenneth

AU - Selfors, Laura M

AU - Li, Carman Man-Chung

AU - Boedicker, Mackenzie

AU - Kuiken, Hendrik J

AU - Richardson, Andrea

AU - Brock, Jane

AU - Garber, Judy

AU - Dillon, Deborah

AU - Sachs, Norman

AU - Clevers, Hans

AU - Brugge, Joan S

PY - 2020/4/6

Y1 - 2020/4/6

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.

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.

U2 - 10.1038/s41467-020-15548-7

DO - 10.1038/s41467-020-15548-7

M3 - Article

C2 - 32249764

SN - 2041-1723

VL - 11

SP - 1711

JO - Nature Communications

JF - Nature Communications

IS - 1

ER -

Organoid cultures from normal and cancer-prone human breast tissues preserve complex epithelial lineages

Abstract

Access to Document

Fingerprint

Cite this