Defining a mesenchymal progenitor niche at single-cell resolution

Most vertebrate organs are composed of epithelium surrounded by support and stromal tissues formed from mesenchyme cells, which are not generally thought to form organized progenitor pools. Here, we use clonal cell labeling with multicolor reporters to characterize individual mesenchymal progenitors in the developing mouse lung. We observe a diversity of mesenchymal progenitor populations with different locations, movements, and lineage boundaries. Airway smooth muscle (ASM) progenitors map exclusively to mesenchyme ahead of budding airways. Progenitors recruited from these tip pools differentiate into ASM around airway stalks; flanking stalk mesenchyme can be induced to form an ASM niche by a lateral bud or by an airway tip plus focal Wnt signal. Thus, mesenchymal progenitors can be organized into localized and carefully controlled domains that rival epithelial progenitor niches in regulatory sophistication. Clonal cell labeling with multicolor reporters reveals individual stem cells in the developing mouse lung. [Also see Perspective by Lee and Kim ] Despite the variety of organ systems, there is a common theme: Stromal tissues support and maintain most vertebrate organs. These stromal tissues form from mesenchymal stem cells. Kumar et al. used clonal cell labeling in mice to identify and characterize stromal progenitors in the developing mouse lung at single-cell resolution (see the Perspective by Lee and Kim). Progenitor populations occupied different locations and displayed a variety of movements and lineage boundaries. Airway smooth muscle progenitors are located just ahead of budding branches in the bronchial tree and are organized into carefully controlled domains. Science , this issue 10.1126/science.1258810 ; see also p. 810