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New lung cell type discovered.

Cystic fibrosis is a genetic-based disorder primarily affecting the lungs.  The gene affected by cystic fibrosis is CFTR (cystic fibrosis transmembrane conductance regulator), controlling the movement of electrolytes in and out of cells. People with cystic fibrosis experience a build-up of thick sticky mucus in the lungs, digestive system, and other organs, affecting the entire body.  Treatments are available to help reduce the problems caused by this condition, however, life expectancy is still shortened. Now, a study led by researchers at Harvard Medical School identifies a new, rare type of cell in the human airway, that appears to be the primary regulator of CFTR gene activity.  The team named the newly discovered cells ‘pulmonary ionocytes’, suggesting the majority of CFTR expression occurs in these cells shown to make up around one percent of airway cells.  The study is published in the journal Nature.

Previous studies show CFTR is a protein regulating the balance between salt and water on epithelial surfaces such as those seen in the lung or pancreas. Mutations in CFTR can cause a buildup of thick mucus in the lung, pancreas, and other organs, leading to cystic fibrosis.  Despite decades of study on CFTR and progress in treating cystic fibrosis, there is still no cure.  The current study shows  CFTR activity is concentrated in a small, previously unknown population of cells, serving as promising targets for cystic fibrosis.

The current study utilizes single-cell sequencing technology to analyze gene expression in tens of thousands of individual cells isolated from human and mouse airways.  Comparing patterns of gene expression and using previously described cells as references, the team created comprehensive catalogs of different cell types and states, including their abundance and distribution.  Results show pulmonary ionocytes expressed higher levels of CFTR than any other cell.

Data findings suggest the majority of CFTR expression occurs in pulmonary ionocytes. Results show the activity of CFTR is directly related to the number of pulmonary ionocytes in the tissue.  When the lab disrupted a critical molecular process in pulmonary ionocytes in mice, they observed the onset of key features associated with cystic fibrosis, notably the formation of dense mucus. The group concludes this finding underscores how important these cells are to airway-surface regulation.

The team surmises they have identified a rare cell type, the pulmonary ionocyte, they have shown to be a primary source of activity of the CFTR gene, implicated in cystic fibrosis.  For the future, the researchers state their findings point to new strategies for treating cystic fibrosis, such as increasing the amount of pulmonary ionocytes to raise the amount of CFTR activity.

Source: Harvard Medical School

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