The role of basal cells in attachment of columnar cells to the basal lamina of the trachea.
ABSTRACT The mechanism by which basal cells play a role in attachment of airway epithelium to the basal lamina has not been determined. Our hypothesis is that basal cells form a structural bridge between columnar cells and the basal lamina via hemidesmosomes, the cytoskeleton, and desmosomes. To evaluate this hypothesis, we determined the percentage of the columnar cell surface area associated with attachment to the basal lamina and the basal cell in tracheal epithelia of different heights. Tracheas from mice, hamsters, rats, bonnet monkeys, cats, and sheep were prepared for electron microscopy by standard techniques. The height of the epithelia ranged from 8.6 microns in the hamster to 56.8 microns in the sheep. The number of basal cells/100 microns ranged from 3.4 in the hamster to 21.4 in the sheep. The percentage of the basal lamina covered by basal cells increased from 32.6 in the hamster to 94.7 in the sheep. In the shorter epithelia of the hamster, 32% of the columnar cell attachment to the basal lamina was indirect through basal cells, and in the taller epithelia of the sheep, 92% of the columnar cell attachment was by this means. Conversely, the percentage of columnar cell surface in contact with the basal lamina decreased from 67.4% in the hamster to 5.3% in the sheep. These data demonstrate that basal cells play a role in attachment of columnar epithelium to the basal lamina by presenting a surface area for cell-to-cell attachment, thus acting as a bridge between columnar cells and the basal lamina.
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ABSTRACT: Airways progenitors may be involved in embryogenesis and lung repair. The characterization of these important populations may enable development of new therapeutics to treat acute or chronic lung disease. In this study, we aimed to establish the presence of bronchioloalveolar progenitors in ovine lungs and to characterize their potential to differentiate into specialized cells. Lung cells were studied using immunohistochemistry on frozen sections of the lung. Immunocytochemistry and flow cytometry were conducted on ex-vivo derived pulmonary cells. The bronchioloalveolar progenitors were identified by their co-expression of CCSP, SP-C and CD34. A minor population of CD34pos/SP-Cpos/CCSPpos cells (0.33% +/- 0.31) was present ex vivo in cell suspensions from dissociated lungs. Using CD34 magnetic positive-cell sorting, undifferentiated SP-Cpos/CCSPpos cells were purified (>80%) and maintained in culture. Using synthetic media and various extracellular matrices, SP-Cpos/CCSPpos cells differentiated into either club cells (formerly named Clara cells) or alveolar epithelial type-II cells. Furthermore, these ex vivo and in vitro derived bronchioloalveolar progenitors expressed NANOG, OCT4 and BMI1, specifically described in progenitors or stem cells, and during lung development. We report for the first time in a large animal the existence of bronchioloalveolar progenitors with dual differentiation potential and the expression of specialized genes. These newly described cell population in sheep could be implicated in regeneration of the lung following lesions or in development of diseases such as cancers.BMC Veterinary Research 11/2013; 9(1):224. · 1.86 Impact Factor
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ABSTRACT: Understanding the mechanisms underlying the process of regeneration and repair of airway epithelial structures demands close characterization of the associated cellular and molecular events. The choice of an animal model system to study these processes and the role of lung stem cells is debatable since ideally the chosen animal model should offer a valid comparison with the human lung. Species differences may include the complex three-dimensional lung structures, cellular composition of the lung airway as well as transcriptional control of the molecular events in response to airway epithelium regeneration, and repair following injury. In this paper, we discuss issues related to the study of the lung repair and regeneration including the role of putative stem cells in small- and large-animal models. At the end of this paper, the author discuss the potential for using sheep as a model which can help bridge the gap between small-animal model systems and humans.The Scientific World Journal 01/2012; 2012:961684. · 1.73 Impact Factor
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ABSTRACT: The mechanisms linking systems-level programs of gene expression to discrete cell biological processes in vivo remain poorly understood. In this study, we have defined such a program for multi-ciliated epithelial cells (MCCs), a cell type critical for proper development and homeostasis of the airway, brain and reproductive tracts. Starting from genomic analysis of the cilia-associated transcription factor Rfx2, we used bioinformatics and in vivo cell biological approaches to gain insights into the molecular basis of cilia assembly and function. Moreover, we discovered a previously un-recognized role for an Rfx factor in cell movement, finding that Rfx2 cell-autonomously controls apical surface expansion in nascent MCCs. Thus, Rfx2 coordinates multiple, distinct gene expression programs in MCCs, regulating genes that control cell movement, ciliogenesis, and cilia function. As such, the work serves as a paradigm for understanding genomic control of cell biological processes that span from early cell morphogenetic events to terminally differentiated cellular functions. DOI: http://dx.doi.org/10.7554/eLife.01439.001.eLife. 01/2014; 3:e01439.