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

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 () and Charlotte Kuperwasser ()
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Gat Rauner: Tufts University
Dexter X. Jin: Whitehead Institute for Biomedical Research
Daniel H. Miller: Whitehead Institute for Biomedical Research
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
Yu-Xiong Feng: Whitehead Institute for Biomedical Research
Robert A. Mathis: Whitehead Institute for Biomedical Research
J. Christopher Love: Massachusetts Institute of Technology
Piyush B. Gupta: Tufts University
Charlotte Kuperwasser: Tufts University

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-27401-6

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