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The different epithelial stem/progenitor cells identified so far in the different regions of the lung interact with specific stromal, and physical/mechanical, niches. Some of these niches have recently been characterized. These niches dictate the quiescence of the epithelial stem/progenitor cells, as well as their re-entry into the cell cycle and subsequent differentiation. The mesenchyme, which gives rise to different stromal cell niches has so far been understudied during development, homeostasis, injury/repair and disease development. Similarly, the effects on stem cells of the physical/mechanical properties of their local environment are just beginning to be explored.