Cell Fate Analysis in Fetal Mouse Lung Reveals Distinct Pathways for TI and TII Cell Development.

Cell Fate Analysis in Fetal Mouse Lung Reveals Distinct Pathways for TI and TII Cell Development. Am J Physiol Lung Cell Mol Physiol. 2019 Aug 21;: Authors: Gonzalez R, Leaffer D, Chapin C, Gillespie A, Eckalbar W, Dobbs LG Abstract Alveolar type I (TI) cells are large squamous cells that cover >95% of the internal surface area of the lung; type II (TII) cells are small cuboidal cells with distinctive intracellular surfactant storage organelles. Based on autoradiographic studies in the 1970s, the long-held paradigm of alveolar epithelial development has been a linear progression from undifferentiated progenitor cells through TII cells to TI cells. Subsequent data support the existence of more complex pathways. Recently, a bipotent TI/TII progenitor cell at E18 has been inferred both from marker expression in developing airways and from statistical analyses of gene expression data obtained from single lung embryonic cells. To study cell lineage directly by fate mapping, we developed new transgenic mouse models in which rtTA is driven either by the rat podoplanin or the mouse Sftpc gene to mark cells irreversibly in development. Using these models, we found two distinct lineage pathways. One pathway, evident as early as E12-15, is devoted almost exclusively to TI cell development; a second pathway gives rise predominantly to TII cells but also a subpopulation of TI cells. We have defined the molecular phenotypes of these distinct pr...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - Category: Cytology Authors: Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research