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

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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 (US)
Article number	1711
Journal	Nature communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-15548-7
State	Published - Dec 1 2020
Externally published	Yes

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
General
Physics and Astronomy(all)

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10.1038/s41467-020-15548-7

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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

Rosenbluth, JM, Schackmann, RCJ, Gray, GK, Selfors, LM, Li, CMC, 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, 1711. https://doi.org/10.1038/s41467-020-15548-7

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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.}",

note = "Funding Information: We would like to acknowledge the exceptional team who facilitated tissue acquisition for these studies, including the Brigham and Women{\textquoteright}s Hospital (BWH) breast surgery team led by Tari King, MD, plastic surgery team Indranil Sinha, MD and Bo Pomahac, MD, the BWH Faulkner pathologists led by Stephen Pochebit, MD, and the specimen collection group led by Samantha Stokes and the Breast Biorepository staff. We also thank Amgen for providing RANK antibody (N1H8) for use in the CyTOF experiments, Jon Coloff for providing MCF10A cells grown in 3D culture, Alexis Cook for technical assistance, Angie Martinez Gakidis for critical reading of the manuscript, Wendy Fantl for advice on CyTOF, David Livingston and Shailja Pathania for BRCA1 antibody and immortalized HMECs, Calvin Kuo for R-spondin 1-expressing 293 cells, and The Nikon Imaging Center at Harvard Medical School for assistance with imaging. This work was supported by the grants from the BRCA Foundation, Susan G Komen Foundation, the Gray Foundation and a gift from the Anbinder Fund for Cancer Research to J.S.B., an ACS Postdoctoral Fellowship, a Susan G Komen Foundation award, and an ASCO Young Investigator Award to J.M.R., a F32 fellowship to G.K.G., and a SPORE Grant (1P50CA168504) to Dana-Farber/Harvard Cancer Center, and a Breast Cancer Research Foundation grant to J.G. Publisher Copyright: {\textcopyright} 2020, The Author(s).",

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

language = "English (US)",

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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.

N1 - Funding Information: We would like to acknowledge the exceptional team who facilitated tissue acquisition for these studies, including the Brigham and Women’s Hospital (BWH) breast surgery team led by Tari King, MD, plastic surgery team Indranil Sinha, MD and Bo Pomahac, MD, the BWH Faulkner pathologists led by Stephen Pochebit, MD, and the specimen collection group led by Samantha Stokes and the Breast Biorepository staff. We also thank Amgen for providing RANK antibody (N1H8) for use in the CyTOF experiments, Jon Coloff for providing MCF10A cells grown in 3D culture, Alexis Cook for technical assistance, Angie Martinez Gakidis for critical reading of the manuscript, Wendy Fantl for advice on CyTOF, David Livingston and Shailja Pathania for BRCA1 antibody and immortalized HMECs, Calvin Kuo for R-spondin 1-expressing 293 cells, and The Nikon Imaging Center at Harvard Medical School for assistance with imaging. This work was supported by the grants from the BRCA Foundation, Susan G Komen Foundation, the Gray Foundation and a gift from the Anbinder Fund for Cancer Research to J.S.B., an ACS Postdoctoral Fellowship, a Susan G Komen Foundation award, and an ASCO Young Investigator Award to J.M.R., a F32 fellowship to G.K.G., and a SPORE Grant (1P50CA168504) to Dana-Farber/Harvard Cancer Center, and a Breast Cancer Research Foundation grant to J.G. Publisher Copyright: © 2020, The Author(s).

PY - 2020/12/1

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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.

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

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