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Breast tissue regeneration is driven by cell-matrix interactions coordinating multi-lineage stem cell differentiation through DDR1

Author

Listed:
  • Gat Rauner

    (Tufts University)

  • Dexter X. Jin

    (Whitehead Institute for Biomedical Research
    Massachusetts Institute of Technology)

  • Daniel H. Miller

    (Whitehead Institute for Biomedical Research
    Massachusetts Institute of Technology)

  • Todd M. Gierahn

    (Massachusetts Institute of Technology)

  • Carman M. Li

    (Ludwig Center at Harvard, Harvard Medical School)

  • Ethan S. Sokol

    (Whitehead Institute for Biomedical Research
    Massachusetts Institute of Technology)

  • Yu-Xiong Feng

    (Whitehead Institute for Biomedical Research)

  • Robert A. Mathis

    (Whitehead Institute for Biomedical Research
    Massachusetts Institute of Technology)

  • J. Christopher Love

    (Massachusetts Institute of Technology
    Broad Institute of MIT and Harvard
    Ragon Institute of MGH, MIT and Harvard)

  • Piyush B. Gupta

    (Tufts University
    Whitehead Institute for Biomedical Research
    Massachusetts Institute of Technology
    Tufts University School of Medicine)

  • Charlotte Kuperwasser

    (Tufts University
    Tufts University School of Medicine)

Abstract

Mammary morphogenesis is an orchestrated process involving differentiation, proliferation and organization of cells to form a bi-layered epithelial network of ducts and lobules embedded in stromal tissue. We have engineered a 3D biomimetic human breast that makes it possible to study how stem cell fate decisions translate to tissue-level structure and function. Using this advancement, we describe the mechanism by which breast epithelial cells build a complex three-dimensional, multi-lineage tissue by signaling through a collagen receptor. Discoidin domain receptor tyrosine kinase 1 induces stem cells to differentiate into basal cells, which in turn stimulate luminal progenitor cells via Notch signaling to differentiate and form lobules. These findings demonstrate how human breast tissue regeneration is triggered by transmission of signals from the extracellular matrix through an epithelial bilayer to coordinate structural changes that lead to formation of a complex ductal-lobular network.

Suggested Citation

  • Gat Rauner & Dexter X. Jin & Daniel H. Miller & Todd M. Gierahn & Carman M. Li & Ethan S. Sokol & Yu-Xiong Feng & Robert A. Mathis & J. Christopher Love & Piyush B. Gupta & Charlotte Kuperwasser, 2021. "Breast tissue regeneration is driven by cell-matrix interactions coordinating multi-lineage stem cell differentiation through DDR1," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27401-6
    DOI: 10.1038/s41467-021-27401-6
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    References listed on IDEAS

    as
    1. Devon A. Lawson & Nirav R. Bhakta & Kai Kessenbrock & Karin D. Prummel & Ying Yu & Ken Takai & Alicia Zhou & Henok Eyob & Sanjeev Balakrishnan & Chih-Yang Wang & Paul Yaswen & Andrei Goga & Zena Werb, 2015. "Single-cell analysis reveals a stem-cell program in human metastatic breast cancer cells," Nature, Nature, vol. 526(7571), pages 131-135, October.
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