Accelerate single cell analyses in industry and academia

EuroBiotech_ Dr Schnall-Levin, with its Chromium and Visium platform, 10x Genomics has immensely simplified the feasibility of single cell studies, e.g. of the transcriptome. Could you please give a brief overview and outlook on how and in which fields of application the platforms help to advance translational projects?
Schnall-Levin_Our mission is to master biology to advance human health. We believe that once we understand biology we can effectively treat deadly diseases like cancer, as well as auto-immune, infectious, and neurodegenerative diseases. At 10x Genomics, we’re committed to arming researchers with tools capable of unravelling the complexity of disease at its fundamental unit—the cell. Since the launch of our first product in 2016, we’ve enabled researchers to study gene expression, chromatin landscape, T- and B-cell repertoire sequence, protein expression, and antigen specificity at single cell resolution.
The use of our tools to understand fundamental aspects of diseases is incredibly rewarding, and we are committed to enabling the next generation of translational studies on our platforms. Researchers are harnessing the power of single cell resolution across the translational continuum—from high-throughput functional screens for therapeutic development, to profiling patient samples from clinical trials for biomarker discovery. To date, our technology has been featured in over 2,500 peer-reviewed publications.

EuroBiotech_By combining the Visium platform with the technology of Spatial Transcriptomics, which was acquired in 2018, transcriptional profiles of each individual cell can be assigned to its position in the tissue (e.g. clinical tissue sections). Where do you see the greatest benefit for translational researchers and companies and how do you intend to further develop products for this field of research?
Schnall-Levin_Spatial gene expression is incredibly powerful, and we are in the early days of realizing the potential of this technology. The first applications of spatial sequencing have largely focused on creating atlases of human tissue to understand the spatial niche in which cells reside. In cancer, researchers are discovering physical patterns of colocalization and exclusion within the tumour microenvironment and peripheral tissue that define disease progression – all with high resolution and scale. In neurosciences, the study of neural cells and circuits originated in anatomy, as the spatial architecture of the brain is a critical component of its function. As scientists begin to unravel the mechanisms underlying neurological disease and realize how genetics impact disease pathogenesis and progression, spatial context will be imperative to connect the dots between functional cell states and subtypes revealed by transcriptomics and pathology localized to specific cell types and brain regions. From a therapeutic and biomarker development perspective, it’s powerful to start to define the specific cells and signalling networks that are driving pathology, like metastasis or immune exclusion from the tumour microenvironment, for example, and to correlate these with therapeutic response.

EuroBiotech_While single-cell technologies tend to be used in a low-throughput manner in academic or translational settings by their very nature, the level of automation is usually much higher for drug developers. How do you try to meet these different needs?
Schnall-Levin_At 10x Genomics, we are committed to innovation and continuously seek opportunities to push the boundaries of discovery and clinical translation with our technology. Recently, we announced the launch of our new Chromium X instrument and CellPlex solution, the combination of which will enable 1 million cell experiments. The ability to profile more samples and more cells simultaneously will be especially impactful for profiling larger patient cohorts in translational studies and increasing the scale of functional screens for drug development. We also know that automation is an important component of scaling single cell experiments, and we continue to enable the automation of new single cell workflows on our Chromium Connect instrument.Aside from scale, we’re expanding the range of sample inputs possible across our Chromium single cell and Visium spatial platforms, specifically with the goal of assessing challenging clinical sample types. We recently launched our Visium solution for FFPE, and will be enabling single cell RNA sequencing compatibility with fixed cells in the later half of 2021. We are also developing software tools to make the interpretation of single cell data faster, more accessible, and more collaborative across disciplines and disparate research teams with our 10x Cloud Analysis platform.

EuroBiotech_Which applications of your techniques in translational research do you currently find most exciting?
Schnall-Levin_It’s difficult to choose just a few examples of translational applications that we’re excited about. This past year, it’s been remarkable to see the use of single cell profiling in COVID-19 research to understand the complex coordination of innate and adaptive immune cell populations across stages of disease severity. These findings are pivotal in therapeutic development, detection of new biomarkers to support prognostic decisions, and discovery of new therapeutic antibodies. Research groups from Stanford and Emory universities compiled a comprehensive atlas of the immune response in COVID-19 patients, including single cell RNA and protein expression, to reveal mechanisms of infection and potential therapeutic targets. They found that there is an impaired interferon (IFN) response in COVID-19 patients and propose testing IFN as a therapy. There are now clinical trials underway testing whether IFN therapy can be used to treat COVID-19 patients. In cancer, we’re seeing single cell multiomics uncovering a new understanding of the mechanisms of response, resistance, and toxicity in immunotherapies like checkpoint inhibitors, CAR-T, and cancer vaccines. Recently, there was a groundbreaking study from Stanford that used single cell RNA sequencing to uncover why some patients undergoing CD19 CAR-T therapy experience severe neurotoxic side effects after infusion—the mechanism of which has remained elusive in the field for a decade. The team discovered an ultra-rare population of cells lining the blood-brain barrier that express CD19, suggesting a mechanism behind CD19 CAR-T cell trafficking to the brain. This study shows the value of creating atlases of single cell expression data across all tissues to anticipate on-target, off-tissue toxicities for cell therapies.

Dr Michael Schnall-Levin is Founding Scientist of 10x Genomics and has been at the company since its inception and today serves as Senior Vice President, R&D. Before joining 10x Genomics, Michael was a NSF postdoctoral fellow with Eric Lander at the Broad Institute, where he worked on developing novel applications of DNA sequencing technologies. Prior to that, Michael worked at Foundation Medicine, where he developed some of the early algorithms to accurately detect mutations in patient tumor samples. Michael earned his Ph.D in Mathematics from MIT with Bonnie Berger, where he was both a Hertz fellow and NDSEG fellow, and his B.A. in Physics from Harvard College.

This interview was originally published in Summer Edition European Biotechnology Magazine 2021.