Whenever we breathe in and out, complex things happen in the lung: Around 40 highly specialized cell types work together to ensure that gas exchange works perfectly. The team of Dr. Herbert Schiller, DZL young investigator group leader at the Institute of Lung Biology and Disease and Prof. Fabian Theis, DZL-PI and director of the Institute for Computational Biology at the Helmholtz Zentrum München, wanted to find out:
What are we dealing with at the cellular level when lung function declines in old age? What changes in the cells, what imbalances are observed, and what triggers them?
To answer these questions, the DZL researchers combined different approaches:
• Broad genomic analysis of single cells
• Biochemical analysis of all proteins in the lung (proteomics)
• Machine Learning / Artificial Intelligence based data analysis
The Cell Biology Approach: With single cell transcriptomics, the researchers analyzed the activity of genes in about 30 different cell types of the lung, at different ages. The observed changes were then ascribed to the proteins produced by the genes.
At this point, the Artificial Intelligence approach was brought in: The scientists around Fabian Theis developed algorithms to better understand the structure of the data and unveil the biology hidden inside. After the data had been meaningfully brought together and interpreted, the first fascinating findings were observed.
Aged lung cells - less active and influenced by the environment
Herbert Schiller explains that, with increasing age, genes in the cells of the lung apparently no longer work at the same coordinated rate: "Although a particular cell type in younger lungs will control its gene activity precisely, the gene activity and hence identity of older lung cells, is less constant." Cells of the same cell type have differential gene activity between young and old- and so the “lung machine” breaks down ...
Epigenetics also plays a role, according to the researchers. This means that with increasing age, influences from outside of the cell change the DNA within the cell. This too, could disrupt the coordination of gene activity in the lung cells.
The two scientists have made the data freely accessible for colleagues who might be interested.
In cooperation with international research associations, these first results are now being followed by further intensive biological investigations of human lung cells. The aim is a complete mapping of all the cells in the lung within the "Human Cell Atlas":
Human Cell Atlas - International project for the mapping of cells
In the future, the cell atlas of the lung will be included in the Human Cell Atlas (HCA), a sort of Google Maps of the human body. To do this, cells and tissues are "mapped" at different time points, as a reference database for future research and the development of personalized therapies. Leading scientists launched the HCA in 2016, with researchers from more than 60 countries participating. Herbert Schiller focuses specifically on lung-related issues within the HCA consortium and has also co-authored the corresponding white paper for the Human Cell Atlas.
More about the Human Cell Atlas can be found here.
Dr. Herbert Schiller
Dr. Fabian Theis
Tel.: +49 89 3187-1194
Helmholtz Zentrum München
Institute of Lung Biology and Disease
Lukas Simon, Postdoc
Ilias Angelidis, Doctoral Student
Maximilian Strunz, Doctoral Student
Meshal Ansari, Doctoral Student
Pawandeep Singh, Master Student
Mert Akgündüz, Master Student
Laura Mattner, Doctoral Student
Paulina Ogar, Master Student
Christoph Mayr, Doctoral Student
Angelidis, I. et al, Nature Communications, 2019:
An atlas of the aging lung mapped by single cell transcriptomics and deep tissue proteomics.
Schiller, H. et al, American Journal of Respiratory Cell and Molecular Bilogy, 2019
The Human Lung Cell Atlas - A high-resolution reference map of the human lung in health and disease