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Asthma treatment hope as Human Cell Atlas project creates first map of lungs




The building blocks of human lungs and airways have been mapped by researchers for the first time.

Dr Sarah Teichmann FMedSci, Cellular Genetics Programme Head, WTSI,in front of the computer cluster at Sanger. Picture: Pari Naderi. (12569153)
Dr Sarah Teichmann FMedSci, Cellular Genetics Programme Head, WTSI,in front of the computer cluster at Sanger. Picture: Pari Naderi. (12569153)

The work, by scientists at the Wellcome Sanger Institute, University Medical Center Groningen, Open Targets, GSK and collaborators, forms part of the Human Cell Atlas - an ambitious global project to create a cellular map of the entire body.

They plotted the cells in the lungs of both asthma patients and those without the condition. This helped to illustrate the differences in asthmatic and normal airways, demonstrated how cells in the lung communicate with each other and led to a new discovery.

Dr Felipe Vieira Braga, a first author on the paper from the Wellcome Sanger Institute and Open Targets, explained: “We have generated a detailed anatomical map of the respiratory airways. This has given us a better definition of the cell types in asthmatic lungs, and allowed us to discover an entirely new cell state in asthmatic patients that produces mucus.”

Asthma affects more than 350 million people worldwide, with more than five million receiving treatment for it in the UK alone.

While it is often manageable with medication, it can cause ongoing problems and there is a risk of severe, life-threatening asthma attacks.

Dr Sarah Teichmann, a senior author from the Wellcome Sanger Institute, University of Cambridge and Open Targets, and co-chair of the Human Cell Atlas Organising Committee, said: “Our large-scale, open access data reveals the activity of different cells, their communication pathways and locations. The lung cell atlas will provide a great resource for further lung research and we hope that it will enable the identification of potential new therapeutic targets for asthma relief.”

Researchers used single cell technology to study samples from 17 people, and analysed more than 36,000 individuals cells from the nasal area and three different areas of the lung.

This enabled them to see which genes were active in each cell and identify the specific cell type.

They then detected different cell types and activities in lung samples from six asthma patients and compared them to normal lungs, which highlighted clear differences.

A symptom of asthma is the overproduction of mucus, but not all the cells responsible for itwere known.

an airway wall biopsy from a patient with chronic obstructive pulmonary disease. Image: Prof Wim Timens, UMCG (12569145)
an airway wall biopsy from a patient with chronic obstructive pulmonary disease. Image: Prof Wim Timens, UMCG (12569145)

The research, published in Nature Medicine, describes a newly-discovered mucus-creating cell state - called the muco-cilliated state - in asthmatic lungs.

Asthmatic lungs also had many more inflammatory Th2 cells, which sent the vast majority of cellular signals in asthma, while normal lungs used a broad range of cell communications.

Dr Martijn Nawijn, a senior author from University Medical Center Groningen, said: “We already knew that inflammatory Th2 cells played a role in asthma, but only now do we see how great that influence is.

“In normal people, all kinds of cells communicate with each other in order to keep the airways functioning well. But in asthma patients, almost all of those interactions are lost. Instead of a network of interactions, in asthma the inflammatory cells seem to completely dominate the communication in the airways.”

Understanding these processes could be key in finding new drug targets that could prevent cells from responding to inflammatory signals.

Further implications for the study of drug targets and design of drug trials were uncovered. The atlases demonstrated thatlocation is important for lung cells, with cells in different areas having very different activities.

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