Department of Developmental, Chemical & Molecular Biology, Tufts University, Boston, MA, 02111, USA.
Whitehead Institute for Biomedical Research, Cambridge, MA, 02142, USA.
Nat Commun. 2021 Dec 10;12(1):7116. 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.
乳腺形态发生是一个协调的过程，涉及细胞的分化、增殖和组织，以形成一个双层上皮网络的导管和小叶嵌入在基质组织中。我们已经设计了一种 3D 仿生人类乳房，使研究干细胞命运决定如何转化为组织水平的结构和功能成为可能。利用这一进展，我们描述了通过胶原蛋白受体信号传递，乳腺上皮细胞如何构建复杂的三维多谱系组织的机制。Discoidin 结构域受体酪氨酸激酶 1 诱导干细胞分化为基底细胞，基底细胞通过 Notch 信号转导反过来刺激腔前体细胞分化并形成小叶。这些发现表明，人类乳腺组织再生是如何通过细胞外基质通过上皮双层传递信号来触发的，以协调导致形成复杂的导管小叶网络的结构变化。
