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

• Published in: Nature communications Vol. 12; no. 1; p. 7116
• Main Authors: Rauner, Gat, Jin, Dexter X., Miller, Daniel H., Gierahn, Todd M., Li, Carman M., Sokol, Ethan S., Feng, Yu-Xiong, Mathis, Robert A., Love, J. Christopher, Gupta, Piyush B., Kuperwasser, Charlotte
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.12.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/106; 13/109; 13/31; 13/44; 13/51; 14/1; 14/19; 14/35; 38; 49; 631/136/532/489; 631/532/2436; 631/61/54/2295; 631/80/86/820; 639/166/985; 82/1; 82/80; 96; Basal cells; Biocompatible Materials; Biomedical Engineering; Biomimetics; Breast; Breast - cytology; Breast - physiology; Cell Communication - physiology; Cell differentiation; Cell Differentiation - physiology; Cell fate; Cell Line; Cell proliferation; Collagen; Differentiation (biology); Discoidin Domain Receptor 1 - genetics; Discoidin Domain Receptor 1 - metabolism; Epithelial cells; Epithelial Cells - cytology; Epithelium; Extracellular Matrix; Humanities and Social Sciences; Humans; Kinases; Morphogenesis; multidisciplinary; Multilayers; Progenitor cells; Progeny; Protein-tyrosine kinase receptors; Receptors; Regeneration; Science; Science (multidisciplinary); Signal Transduction; Signaling; Stem cells; Stem Cells - cytology; Structure-function relationships; Tissue engineering; Tissues; Tyrosine
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-27401-6

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. Mammary morphogenesis is a complex process. Here the authors describe how stem cells build a three-dimensional self-organizing multi-lineage tissue by showing that positional signals from the extracellular matrix through the collagen receptor DDR1 lead stem cells to differentiate into multi-lineage committed multi-layered progeny.