Alveolar cell fate selection and lifelong maintenance of AT2 cells by FGF signaling.

The lung's gas exchange surface is comprised of alveolar AT1 and AT2 cells that are corrupted in several common and deadly diseases. They arise from a bipotent progenitor whose differentiation is thought to be dictated by differential mechanical forces. Here we show the critical determinant is FGF signaling.

Transient external force induces phenotypic reversion of malignant epithelial structures via nitric oxide signaling.

Non-malignant breast epithelial cells cultured in three-dimensional laminin-rich extracellular matrix (lrECM) form well organized, growth-arrested acini, whereas malignant cells form continuously growing disorganized structures. While the mechanical properties of the microenvironment have been shown to contribute to formation of tissue-specific architecture, how transient external force influences this behavior remains largely unexplored. Here, we show that brief transient compression applied to single malignant breast cells in lrECM stimulated them to form acinar-like structures, a phenomenon we term 'mechanical reversion.

Single-cell Wnt signaling niches maintain stemness of alveolar type 2 cells.

Alveoli, the lung's respiratory units, are tiny sacs where oxygen enters the bloodstream. They are lined by flat alveolar type 1 (AT1) cells, which mediate gas exchange, and AT2 cells, which secrete surfactant. Rare AT2s also function as alveolar stem cells.

Alveolar progenitor and stem cells in lung development, renewal and cancer.

Alveoli are gas-exchange sacs lined by squamous alveolar type (AT) 1 cells and cuboidal, surfactant-secreting AT2 cells. Classical studies suggested that AT1 arise from AT2 cells, but recent studies propose other sources. Here we use molecular markers, lineage tracing and clonal analysis to map alveolar progenitors throughout the mouse lifespan.

Patterned collagen fibers orient branching mammary epithelium through distinct signaling modules.

For decades, the work of cell and developmental biologists has demonstrated the striking ability of the mesenchyme and the stroma to instruct epithelial form and function in the mammary gland, but the role of extracellular matrix (ECM) molecules in mammary pattern specification has not been elucidated. Here, we show that stromal collagen I (Col-I) fibers in the mammary fat pad are axially oriented prior to branching morphogenesis. Upon puberty, the branching epithelium orients along these fibers, thereby adopting a similar axial bias.