The role of Scgb1a1+ Clara cells in the long-term maintenance and repair of lung airway, but not alveolar, epithelium

By E. Rawlins, T. Okubo, Yan Xue, D. Brass, R. Auten, H. Hasegawa, Fan Wang, B. Hogan. Cell Stem Cell, 2009

836 citations recorded by the source corpus.

Summary To directly test the contribution of Scgb1a1+ Clara cells to postnatal growth, homeostasis and repair of lung epithelium, we generated a Scgb1a1-CreERTM “knock-in” mouse line for lineage tracing these cells. Under all conditions tested the majority of Clara cells in the bronchioles both self-renew and generate ciliated cells. In the trachea, Clara cells give rise to ciliated cells but do not self-renew extensively. Nevertheless, they can contribute to tracheal repair. In the postnatal mouse lung it has been proposed that bronchioalveolar stem cells (BASCs) which co-express Scgb1a1 (Secretoglobin1a1) and SftpC (Surfactant Protein C), contribute descendants to both bronchioles and alveoli. The putative BASCs were lineage labeled in our studies. However, we find no evidence for the function of a special BASC population during postnatal growth, adult homeostasis or repair. Rather, our results support a model in which the trachea, bronchioles and alveoli are maintained by distinct populations of epithelial progenitor cells.

Subfields: Nutrition and Dietetics, Pulmonary and Respiratory Medicine, Surgery

View Paper: https://www.semanticscholar.org/paper/097b02334294ae8a04fb201c8c98fcae5589ddea

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Nutrition and Dietetics

1. B. Hogan
2. P. Noble
3. Jiurong Liang

In Pulmonary and Respiratory Medicine

1. Hans Clevers
2. B. Hogan
3. J. Rock
4. E. Morrisey
5. P. Noble
6. B. Stripp
7. C. E. Barkauskas
8. S. Randell

In Surgery

1. Hans Clevers
2. B. Hogan

Citations in the corpus

• Tracking adult stem cells (2011, background): “Kim et al , 2005 ), but genetic labelling of bronchioalveolar stem cells and columnar Clara cells revealed no contribution to alveoli lineages during normal homeostasis and regeneration”
• Preparing for the First Breath: Genetic and Cellular Mechanisms in Lung Development (2010, methodology): “Using this approach, Rawlins et al. (2009a) have provided good evidence that some individual cells in the early tips are multipotent and can give rise to daughters in both the airways and alveoli.”
• Multiple stromal populations contribute to pulmonary fibrosis without evidence for epithelial to mesenchymal transition (2011, methodology): “This finding is inmarked contrast to the results previously reported after injury induced by hyperoxia and naphthalene (41).”
• Airway basal stem cells: a perspective on their roles in epithelial homeostasis and remodeling (2010, background): “to ciliated cells (Rawlins et al., 2009) and, based on studies in the mouse”
• Basal cells as stem cells of the mouse trachea and human airway epithelium (2009, background): “We currently favor the second model because it is supported by tritiated thymidine pulse-chase experiments in the rat (1) and our own pulse-chase lineage labeling studies with Scgb1a1-CreER (Clara) cells in the mouse trachea (13).”
• Repair and regeneration of the respiratory system: complexity, plasticity, and mechanisms of lung stem cell function (2014, methodology): “…and alveoli is quite different between mouse and human lungs (Figure 1) Turnover of mouse bronchiolar epithelium is normally quite low but lineage tracing studies have established that Scgb1a1+ cells do self-renew and give rise to ciliated cells over the long term (Rawlins et al., 2009b).”