Single Cell Genomics

First symposium of the DZL 3.0 working group with top international researchers

Activity of individual genes in different cells of the developing human lung by `single molecule fluorescent in situ hybridization - smFISH´ (© and data: Christos Samakovlis - SciLifeLab Stockholm)

 

The still relatively young field of single cell genomics - i. e. the massive parallel sequencing of the RNA of hundreds of thousands of individual cells of a tissue or organ - has led to groundbreaking discoveries in biomedical research in recent years and has virtually transformed our understanding of the cellular mechanisms of diseases. It was therefore no surprise that there was great interest in the kick-off meeting of the DZL Single Cell Genomics Working Group of the German Center for Lung Research. More than 100 DZL researchers attended the symposium held via Zoom and contributed to the lively discussions. The symposium was organized by Herbert Schiller (ILBD/CPC-M, Helmholtz Zentrum München) together with Christos Samakovlis (SciLifeLab Stockholm, UGLMC Giessen), both DZL Principal Investigators.

The event started with the eagerly awaited keynote lecture by Peter Dorfmüller (Pathology, University of Giessen). He guided the participants through the variety of microscopic changes in different lung diseases such as pulmonary hypertension, COVID19 and pulmonary fibrosis he and his fellow pathologist observe when studying tissue sections. These microscopic changes typically reflect structural changes in lung tissue. First applications of single cell genomics have already provided first insights into specific changes in gene expression of those cells, that have already catched the eyes of pathologists for many years, due to their changes in size, shape or numbers. Nevertheless, major efforts by interdisciplinary research groups will still be required to simultaneously the gene expression profile and the exact location of single cells within a tissue. Further talks by Martin Nawijn (UGMC Groningen), Alexander Misharin (Northwestern University Chicago), and Susanne Herold (University of Giessen, UGMLC/DZL), among others, introduced the international 'Human (Lung) Cell Atlas' project and showed how novel organoid models, may help to study various human diseases in miniature human organs instead of animal models of human cell lines.

The recurring theme of the online symposium and at the center of many lively discussions was the combination of single cell genomics data with high-resolution imaging. A particularly exciting talk was given by Willi Wagner (University of Heidelberg, TLRC/DZL). He presented recent advances in the generation of extremely highresolution X-ray tomography images of the human lung. The X-ray tomography images he showed achieve magnification and resolution comparable to classical microscopy images, but of the entire lung - and in 3 dimensions. Unsurprisingly, his images caused great enthusiasm among his fellow participating DZL researchers. Joakim Lundeberg’s (SciLifeLab, Stockholm) talk on Spatial Transcriptomics technology developed by his research group - i.e. the assignment of individual cells with a specific gene expression profile to specific locations on microscopic images - likewise resulted in a lively discussion about the possibilities and weaknesses of their new technology.

The symposium also took into account the fact that the analysis and evaluation of single cell genomics is playing an increasingly important role by dedicating a separate session to this topic. The two speakers and DZL PIs Malte Lücken and Fabian Theis (ICB, Helmholtz Zentrum München) demonstrated the possibilities of pooling and jointly analyzing single cell genomics data from different studies or clinical cohorts in combination with demographic data. This allows researchers to distinguish between cellular changes in the lung occuring physiologically during as part of healthy aging process and pathological changes characterizing early or late stages of a particular disease. It became clear that in the future the DZL's Biobanking & Data Management platform as well as the DZL data warehouse will play a key role in future projects such as integrated analysis of single cell genomics data from different clinical cohorts and clinical electronic medical records.

The kick-off meeting showed that single cell genomics plays a key role lung research: "Cellular circuits consisting of multiple individual cells and the gene programs controlling them, act as a functional unit, and are the key to detecting the state of a tissue and predicting its future state or intervening therapeutically.", according to Herbert Schiller, Co-organizer of the DZL single cell genomics working group.

Background:
The new DZL 3.0 funding period for the first time encourages researchers to investigate different lung disease in a cross-disciplinary and comparative manner using the new capabilities of single-cell genomics. The goal: Research groups that normally work on different lung diseases will cooperate closely in the application of new single cell genomics methods and algorithms and gain new insights by comparing the diseases.