Fig. 1

Selected putative niche-stem cell interactions in lung repair/regeneration. 1 Fibroblasts upregulate the expression of IL-6 following injury of the airway epithelium to promote ciliated cell differentiation from basal stem cells in mice [38]. 2 Human airway basal stem cells secrete VEGF to simulate endothelial cells that, in turn, support basal stem cells [43]. 3 Variant Club cells are found adjacent to neuroepithelial bodies and repopulate simple columnar airway epithelia following injury in mice [46–48]. 4 Parabronchial smooth muscle cells secrete FGF10 following airway injury to promote the activation of variant Club cells in mice [51]. 5 BASCs secrete Bmp4 to activate calcineurin/NFAT-c1 signaling in endothelial cells that, in turn, secrete Tsp1 to promote alveolar differentiation of BASCs in mice [53]. 6 (Lipo)fibroblasts are required for the growth of mouse and human AEC2 in vitro [20]. Evidence suggests that these cells give rise to myofibroblasts that are critical for compensatory lung growth following pneumonectomy [57]. 7a. Platelet derived SDF-1 promotes the production of MMP14 in endothelial cells following pneumonectomy in mice [64]. 7b MMP14 activates EGF-like growth factors sequestered in the matrix to promote the activation of AEC2s [63]. 8 Myeloid cells are critical for the resolution of bleomycin-induced pulmonary fibrosis in mice [70]. The proliferation of AEC2 and compensatory growth following pneumonectomy is impaired in mice with insufficient numbers of myeloid cells in the lung ([72] and our unpublished data)