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Construction of developmental lineage relationships in the mouse mammary gland by single-cell RNA profiling

Author

Listed:
  • Bhupinder Pal

    (The Walter and Eliza Hall Institute of Medical Research
    The University of Melbourne)

  • Yunshun Chen

    (The University of Melbourne
    The Walter and Eliza Hall Institute of Medical Research)

  • François Vaillant

    (The Walter and Eliza Hall Institute of Medical Research
    The University of Melbourne)

  • Paul Jamieson

    (The Walter and Eliza Hall Institute of Medical Research)

  • Lavinia Gordon

    (The Walter and Eliza Hall Institute of Medical Research)

  • Anne C. Rios

    (The Walter and Eliza Hall Institute of Medical Research
    The University of Melbourne)

  • Stephen Wilcox

    (The Walter and Eliza Hall Institute of Medical Research)

  • Naiyang Fu

    (The Walter and Eliza Hall Institute of Medical Research
    The University of Melbourne)

  • Kevin He Liu

    (The Walter and Eliza Hall Institute of Medical Research)

  • Felicity C. Jackling

    (The Walter and Eliza Hall Institute of Medical Research)

  • Melissa J. Davis

    (The Walter and Eliza Hall Institute of Medical Research
    The University of Melbourne)

  • Geoffrey J. Lindeman

    (The Walter and Eliza Hall Institute of Medical Research
    The University of Melbourne
    The Royal Melbourne Hospital and Peter MacCallum Cancer Centre)

  • Gordon K. Smyth

    (The Walter and Eliza Hall Institute of Medical Research
    The University of Melbourne)

  • Jane E. Visvader

    (The Walter and Eliza Hall Institute of Medical Research
    The University of Melbourne)

Abstract

The mammary epithelium comprises two primary cellular lineages, but the degree of heterogeneity within these compartments and their lineage relationships during development remain an open question. Here we report single-cell RNA profiling of mouse mammary epithelial cells spanning four developmental stages in the post-natal gland. Notably, the epithelium undergoes a large-scale shift in gene expression from a relatively homogeneous basal-like program in pre-puberty to distinct lineage-restricted programs in puberty. Interrogation of single-cell transcriptomes reveals different levels of diversity within the luminal and basal compartments, and identifies an early progenitor subset marked by CD55. Moreover, we uncover a luminal transit population and a rare mixed-lineage cluster amongst basal cells in the adult mammary gland. Together these findings point to a developmental hierarchy in which a basal-like gene expression program prevails in the early post-natal gland prior to the specification of distinct lineage signatures, and the presence of cellular intermediates that may serve as transit or lineage-primed cells.

Suggested Citation

  • Bhupinder Pal & Yunshun Chen & François Vaillant & Paul Jamieson & Lavinia Gordon & Anne C. Rios & Stephen Wilcox & Naiyang Fu & Kevin He Liu & Felicity C. Jackling & Melissa J. Davis & Geoffrey J. Li, 2017. "Construction of developmental lineage relationships in the mouse mammary gland by single-cell RNA profiling," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01560-x
    DOI: 10.1038/s41467-017-01560-x
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    Cited by:

    1. 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.
    2. Xiaokang Yu & Xinyi Xu & Jingxiao Zhang & Xiangjie Li, 2023. "Batch alignment of single-cell transcriptomics data using deep metric learning," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. 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.
    4. 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.
    5. Clare A. Rebbeck & Jian Xian & Susanne Bornelöv & Joseph Geradts & Amy Hobeika & Heather Geiger & Jose Franco Alvarez & Elena Rozhkova & Ashley Nicholls & Nicolas Robine & Herbert K. Lyerly & Gregory , 2022. "Gene expression signatures of individual ductal carcinoma in situ lesions identify processes and biomarkers associated with progression towards invasive ductal carcinoma," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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