A cell type observed in airway tissues appears to play a central role in the onset of cystic fibrosis, better known as cystic fibrosis. Explanations.
Called pulmonary ionocytes, these cells seem to be the main source of activity of the CFTR gene (transmembrane conductance regulator of cystic fibrosis), whose mutations are known to cause cystic fibrosis.
Despite decades of research on this gene and some progress in treating the disease, there is still no cure.
As researchers strive to find ways to treat cystic fibrosis, it is essential to know that the solution is found in about 1% of the cell population.
Allon Klein, doctor at the Harvard Medical School
In addition, researchers have also characterized other types of rare and poorly understood cells, expanding our understanding of lung biology and related diseases.
Cystic fibrosis is a well-studied disease, but deepening our new knowledge of biology may change the way we approach it. […] We now have the setting for a new cellular account of lung diseases.
Jayaraj Rajagopal, Physician at Harvard University School of Medicine
Using single-cell sequencing technology, two US research teams analyzed gene expression in tens of thousands of individual cells isolated from the respiratory tract of humans and mice.
By comparing gene expression patterns, and using the cells previously described as references, researchers have created comprehensive catalogs of different cell types and states, including their abundance and distribution.
Thus, they mapped the known cell types, but also those that were unknown to medicine, such as pulmonary ionocytes. The researchers were surprised to find that they expressed higher CFTR levels than those of other cell types.
These pulmonary ionocytes appear to play an important role in a process that clears mucus from the airways.
First observed in the 1980s, CFTR encodes a protein that transports chloride ions across cell membranes.
Mutations in this gene can cause thick mucus to accumulate on the walls of the lungs, pancreas, and other organs, and cause frequent respiratory infections and other characteristic symptoms of cystic fibrosis.
For a long time, researchers thought that the CFTR gene was expressed at low levels in hair cells in the airways.
However, the present work shows that the expression of CFTR occurs largely in pulmonary ionocytes, which represent only about 1% of airway cells.
In addition, researchers have shown that gene activity, and not just its expression, is related to the number of lung ionocytes in the tissues.
Thanks to technology and efforts to map cell types in different tissues, we are making new discoveries, like cells we did not know existed, of cell subtypes that are rare or have not been noticed before, even in systems that have been studied for decades.
Aviv Regev, Harvard University
Towards a new angle of attack
“The present findings point to new strategies for treating cystic fibrosis, such as increasing the amount of pulmonary ionocytes to promote CFTR activity,” says Aron Jaffe of Harvard University.
In addition, the discovery of these cells can also help guide teams attempting to use gene therapy to correct CFTR mutations.
The details of this work are described in two studies published in Nature magazine .