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

Author

Listed:
  • Jennifer M. Rosenbluth

    (Harvard Medical School)

  • Ron C. J. Schackmann

    (Harvard Medical School)

  • G. Kenneth Gray

    (Harvard Medical School)

  • Laura M. Selfors

    (Harvard Medical School)

  • Carman Man-Chung Li

    (Harvard Medical School)

  • Mackenzie Boedicker

    (Harvard Medical School)

  • Hendrik J. Kuiken

    (Harvard Medical School)

  • Andrea Richardson

    (Brigham & Women’s Hospital)

  • Jane Brock

    (Brigham & Women’s Hospital)

  • Judy Garber

    (Dana-Farber Cancer Institute)

  • Deborah Dillon

    (Brigham & Women’s Hospital)

  • Norman Sachs

    (Hubrecht Institute)

  • Hans Clevers

    (Hubrecht Institute)

  • Joan S. Brugge

    (Harvard Medical School)

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.

Suggested Citation

  • 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 & Debo, 2020. "Organoid cultures from normal and cancer-prone human breast tissues preserve complex epithelial lineages," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15548-7
    DOI: 10.1038/s41467-020-15548-7
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    Cited by:

    1. Maryam Ghaderi Najafabadi & G. Kenneth Gray & Li Ren Kong & Komal Gupta & David Perera & Huw Naylor & Joan S. Brugge & Ashok R. Venkitaraman & Mona Shehata, 2023. "A transcriptional response to replication stress selectively expands a subset of Brca2-mutant mammary epithelial cells," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Maria Fankhaenel & Farahnaz S. Golestan Hashemi & Larissa Mourao & Emily Lucas & Manal M. Hosawi & Paul Skipp & Xavier Morin & Colinda L.G.J. Scheele & Salah Elias, 2023. "Annexin A1 is a polarity cue that directs mitotic spindle orientation during mammalian epithelial morphogenesis," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    3. Yeo-Jun Yoon & Donghyun Kim & Kwon Yong Tak & Seungyeon Hwang & Jisun Kim & Nam Suk Sim & Jae-Min Cho & Dojin Choi & Youngmi Ji & Junho K. Hur & Hyunki Kim & Jong-Eun Park & Jae-Yol Lim, 2022. "Salivary gland organoid culture maintains distinct glandular properties of murine and human major salivary glands," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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