GSE162296
Breast tissue regeneration is driven by cell-matrix interactions that coordinate multi-lineage stem cell differentiation through DDR1
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 storm 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 functions. Using this advancement, we describe the mechanism by which breast epithelial cells build a complex three-dimensional, multi-lineage tissue by signaling through the collagen receptor DDR1. DDR1 induces stem cells to differentiate into basal cells, which in turn stimulate luminal progenitor cells to differentiate and form lobules via Notch signaling. 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 form a complex ductal-lobular network. More broadly, these findings suggest that DDR1 may coordinate collagen and Notch signaling to regulate multi-lineage differentiation and morphogenesis across diverse tissues. Overall design: Single-cell RNA sequencing experiments of mammary organoids treated with or without DDR1 inhibition