ABSTRACT
The search for stem cells in every tissue and organ has become a subject of intense investigation in recent years and has led to new insights into how tissue lineages are derived and how tissues and organs are repaired following injury. Lung stem cells have been sought and a number of potential progenitor phenotypes identified. Interestingly, the resulting studies have indicated stem cells residing in several niches and with different properties and pluripotency. Studies on the pulmonary neuroendocrine cell system (PNEC) which includes single cells as well as PNEC clusters, neuroepithelial bodies (NEB), have yielded clear indication that NEB harbor progenitors and that PNEC may derive from a possible common undifferentiated but committed neuroepithelial like progenitor. What then directs these cells to become neuroendocrine and non-neuroendocrine is not yet fully understood, although early expression of neurogenic genes suggests distinct transcriptional programming. In this review we lay the groundwork for further investigations that may lead to better understanding of lung development and how the PNEC relate to other lung phenotypes. From an ontological point of view, organisms that ‘breathe utilize PNEC as their environmental sensors which are located within an epithelium that subserves transport functions. PNEC/NEB produce a variety of bioactive substances that help to maintain and modulate the surrounding epithelium and the invested connective tissue. The complex role of PNEC/NEB in lung is underscored by the following observations: i) early differentiation and widespread distribution of PNEC during lung development, it) complex innervation of PNEC/NEB that peak during the neonatal period, and iii) the multitude of bioactive amines and peptides synthesized. There is still much to be learned about these aspects and about the specific PNEC/NEB functions that are required for overall lung function in health and disease.
