Tissue Differentiation of ESC into Lung Cells and Functional Validation
The pulmonary system is composed of a variety of epithelial cell populations residing in distinct anatomical locations. Of these, the alveolar epithelial gas exchange surface consists of two cell types, the type I and type II pneumocytes, also known as alveolar epithelial type I and type II (AEI and AEII) cells, that comprise ~95 % and 5 %, respectively, of the alveolar lining area (Chen et al. 2004). AEI cells, important in the regulation of alveolar fluid balance (Dahlin et al. 2004), are branched cells with cytoplasm extremely attenuated for gas exchange (Weibel 1984). AEII cells are cuboidal cells situated between AEI cells and contain characteristic lamellar bodies and apical microvilli (Weibel 1984). Functions of AEII cells include the secretion and reuptake of pulmonary surfactant (Fehrenbach 2001), regulation of alveolar fluid, and synthesis of immunomodulatory proteins (e.g., surfactant protein (SP)-A, SP-D) important for host defense (Matthay et al. 2002). The non-ciliated columnar Clara cells (Evans et al. 1978) constitute the majority of the bronchiolar and terminal bronchiolar epithelium. Clara cells actively divide and differentiate to form ciliated cells, secrete glycosaminoglycans that are major component of the extracellular matrix (ECM), and metabolize airborne toxins by cytochrome P-450 enzymes present in their smooth endoplasmic reticulum (Bishop 2004).
KeywordsIdiopathic Pulmonary Fibrosis Embryoid Body Clara Cell Pluripotent Marker Embryonic Stem Cell Medium
Alveolar epithelial type I
Alveolar epithelial type II
Bronchial epithelial growth medium
Clara cell-specific protein-10
Fluorescence-activated cell sorting
Fibroblast growth factor
Human embryonic stem
Idiopathic pulmonary fibrosis
Lymphoid enhancer factor-1
Quantitative real-time PCR
Small airway growth medium
T cell factor
Transforming growth factor
Vascular endothelial growth factor
We thank Angelique Nelson, Marilyn Nourse, and Carol B. Ware for technical assistance in the culture of hES cells and Bobbie Schneider for technical assistance with the transmission electron microscopy.
Conceived and designed the experiments: ERB, WRH. Performed the experiments: ERB. Analyzed the data: ERB, WRH. Contributed reagents/materials/analysis tools: MAL, TP, MK, CEM. Wrote the paper: ERB, WRH.
The authors have declared that no competing interests exist. This does not alter our adherence to all the PLoS ONE policies on sharing data and materials.
Supported by National Institutes of Health grant R01 HL73722. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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