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Differentiation dynamics of mammary epithelial cells revealed by single-cell RNA sequencing

Author

Listed:
  • Karsten Bach

    (University of Cambridge
    University of Cambridge
    Cancer Research UK Cambridge Cancer Centre)

  • Sara Pensa

    (University of Cambridge
    Cancer Research UK Cambridge Cancer Centre)

  • Marta Grzelak

    (University of Cambridge
    Cancer Research UK Cambridge Cancer Centre)

  • James Hadfield

    (University of Cambridge
    Cancer Research UK Cambridge Cancer Centre)

  • David J. Adams

    (Cancer Research UK Cambridge Cancer Centre
    Wellcome Genome Campus, Hinxton)

  • John C. Marioni

    (University of Cambridge
    Cancer Research UK Cambridge Cancer Centre
    Wellcome Genome Campus, Hinxton
    European Molecular Biology Laboratory)

  • Walid T. Khaled

    (University of Cambridge
    Cancer Research UK Cambridge Cancer Centre)

Abstract

Characterising the hierarchy of mammary epithelial cells (MECs) and how they are regulated during adult development is important for understanding how breast cancer arises. Here we report the use of single-cell RNA sequencing to determine the gene expression profile of MECs across four developmental stages; nulliparous, mid gestation, lactation and post involution. Our analysis of 23,184 cells identifies 15 clusters, few of which could be fully characterised by a single marker gene. We argue instead that the epithelial cells—especially in the luminal compartment—should rather be conceptualised as being part of a continuous spectrum of differentiation. Furthermore, our data support the existence of a common luminal progenitor cell giving rise to intermediate, restricted alveolar and hormone-sensing progenitors. This luminal progenitor compartment undergoes transcriptional changes in response to a full pregnancy, lactation and involution. In summary, our results provide a global, unbiased view of adult mammary gland development.

Suggested Citation

  • Karsten Bach & Sara Pensa & Marta Grzelak & James Hadfield & David J. Adams & John C. Marioni & Walid T. Khaled, 2017. "Differentiation dynamics of mammary epithelial cells revealed by single-cell RNA sequencing," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-02001-5
    DOI: 10.1038/s41467-017-02001-5
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    Cited by:

    1. Ana Sofia Rocha & Alejandro Collado-Solé & Osvaldo Graña-Castro & Jaime Redondo-Pedraza & Gonzalo Soria-Alcaide & Alex Cordero & Patricia G. Santamaría & Eva González-Suárez, 2023. "Luminal Rank loss decreases cell fitness leading to basal cell bipotency in parous mammary glands," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Xing Yang & Haibo Xu & Xu Yang & Hui Wang & Li Zou & Qin Yang & Xiaopeng Qi & Li Li & Hongxia Duan & Xiyun Yan & Nai Yang Fu & Jing Tan & Zongliu Hou & Baowei Jiao, 2024. "Mcam inhibits macrophage-mediated development of mammary gland through non-canonical Wnt signaling," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    3. Maša Alečković & Simona Cristea & Carlos R. Gil Del Alcazar & Pengze Yan & Lina Ding & Ethan D. Krop & Nicholas W. Harper & Ernesto Rojas Jimenez & Donghao Lu & Anushree C. Gulvady & Pierre Foidart & , 2022. "Breast cancer prevention by short-term inhibition of TGFβ signaling," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    4. Alecia-Jane Twigger & Lisa K. Engelbrecht & Karsten Bach & Isabel Schultz-Pernice & Sara Pensa & Jack Stenning & Stefania Petricca & Christina H. Scheel & Walid T. Khaled, 2022. "Transcriptional changes in the mammary gland during lactation revealed by single cell sequencing of cells from human milk," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    5. Naser Ansari-Pour & Yonglan Zheng & Toshio F. Yoshimatsu & Ayodele Sanni & Mustapha Ajani & Jean-Baptiste Reynier & Avraam Tapinos & Jason J. Pitt & Stefan Dentro & Anna Woodard & Padma Sheila Rajagop, 2021. "Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    6. 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.
    7. Elena Spina & Julia Simundza & Angela Incassati & Anupama Chandramouli & Matthias C. Kugler & Ziyan Lin & Alireza Khodadadi-Jamayran & Christine J. Watson & Pamela Cowin, 2022. "Gpr125 is a unifying hallmark of multiple mammary progenitors coupled to tumor latency," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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