VIB team maps each individual fly brain cell throughout the aging process.
Stein Aerts (VIB-KU Leuven Center for Brain & Disease Research) and his team have accomplished a world first: a gene expression map of every cell within the brain of an aging fly. While fly brains are comparatively simple, consisting of only 100,000 different cells, they are still complex networks that aptly serve as models for the human brain. Thus, the atlas is a key step toward a better understanding of human disease development.
Truly understanding an organ – the brain of a fly, in this case – means taking a look at every individual cell that composes it,” Stein asserts. “These cells collaborate to accomplish specific functions, and each expresses a different set of genes, around 15,000 genes in the case of the fruit fly.” To study cell-cell interactions and how they change over time, Stein and his team relied on two cutting-edge technologies, single-sell sequencing and artificial intelligence. These tools enabled the team to examine each cell in detail and process the huge quantities of data needed to understand the activity and function of each cell.
“Sequencing the transcriptomes of 100,000 cells also leads to exciting predictions about the functions of neurons, such as their metabolic activity. The Patrik Verstreken Lab played a crucial role in the in vivo validation of our findings, illustrating the importance of collaborations in these large-scale multidisciplinary projects.”
Stein, your lab is a VIB pioneer in the use of single-cell technologies. Where did your fascination start?
Stein: “We really got interested when two specific papers were published in the same issue of Cell in 2015, which described the use of droplet microfluidics to sequence the RNA of tens of thousands of individual cells in parallel – and more cheaply than ever. We were so excited that we called Jeroen Lammertyn, from the KU Leuven bioengineering faculty, who taught our PhD student Kristofer Davie how to design and fabricate our own microfluidic devices. Our first successful experiment came a few months later – it was a great moment to see cells cluster together as anticipated.”
What do you expect from this technology in your research?
Stein: “Almost all of our research projects, which zoom in on cellular identity at various genetic levels, rely on single-cell resolution. In terms of epigenetics, new technologies will become available at the end of 2018, and we are anticipating an important evolution of single-cell sequencing for those tests as well. Even more, not too far in the future, we’re expecting to see droplet-based single-cell multi-omics technologies – a mouthful of words to describe the enormous power of determining the genome, epigenome, transcriptome and subsets of the proteome from a single cell. This technique will pose challenges for machine-learning techniques, as scientists seek to integrate these multiple layers of information.”
You launched the Fly Cell Atlas (FCA) alongside international colleagues Bart De Plancke, EPFL, and Robert Zinzen, Max Delbruck Center. Has the wider community shown a lot of interest, and how will the platform boost Drosophila research?
Stein: “The FCA platform makes our detailed fly brain data freely available. It’s an online space where scientists can analyze and contribute their data. The community has shown a lot of interest in the FCA, and the wider Drosophila field is keenly focused on developing single-cell atlases, resulting in widespread feedback and collaboration proposals. By mapping all the cells of the fly, we will have a much more thorough understanding of processes occurring during disease development. “We organized the first FCA meeting in Leuven on December 8, 2017, and we’re currently planning the second, to be held at HHMI Janelia Farm in Washington.”
Tell us a little bit more about your new single-cell sequencing data visualization tool. What was the role of the VIB Bioinformatics Core in developing this tool?
Stein: “Maxime De Waegeneer and Kristofer Davie from our lab had developed a prototype of a rapid single-cell visualization app, SCope. Łukasz Kreft from the VIB Bioinformatics Core took interest in the prototype, they co-developed it further and added dozens of new features to make it even more user-friendly. As a result, we developed SCope in just two months – even collaborating between Leuven and Ghent!”
“In the meantime, several other single-cell sequencing projects within VIB have used SCope to visualize their single-cell atlases, such as the lung cancer cell atlas developed by the Diether Lambrechts Lab (VIB-KU Leuven Center for Cancer Biology).”