Understanding biology at the single cell resolution 

Early June saw the gathering of the single cell genomics community at the Wellcome Connecting Science (WCS) Single Cell Biology conference at the WCS Hinxton Hall Conference Centre, based on the Wellcome Genome Campus – in person – for the first time since 2018. The conference also saw the introduction of a hybrid format in the WCS Learning and Training programme – with 149 scientists attending in person and a further 217 participating virtually – it was a truly global conference with representation from 42 different countries, sharing ideas, forming new and consolidating existing collaborations. This gathering was the fourth single cell biology conference – with Ellen Rothenberg (California Institute of Technology, USA), Roser Vento (Wellcome Sanger Institute, UK), Fabian Theis (Technical University of Munich, Germany) and Itai Yanai(NYU Langone Health, USA) serving on the programme committee.

This year’s programme was framed around a set of specific biological questions and challenges that can be interrogated using a single cell approach. These perspectives explored how a cell’s state is influenced by its micro-environment; how cell identity creates morphology; how cell identity is regulated; and, the mechanisms of molecular memory to the dynamics of cell transitions. Designing the conference in this way meant it was interdisciplinary, with contributions from cancer researchers, developmental geneticists, immunologists, and computational biologists all viewing these challenges through the lens of the single cell.

The conference kicked off with a keynote from Aviv Regev, from Genentech, USA, who gave an impressive overview of how cell atlases can be considered as roadmaps to understanding disease. She described how single cell genomics is revealing fundamental features of cells: from the different cell types in a tissue, differentiation, gene programmes, the physical location of cells, and cell interactions. This knowledge enables us to ask and answer important questions in disease like: where do disease risk genes act; which cells are disrupted; which cell programmes are changed; what are their functions and modules; which cellular communications are disrupted; and, what is the effect of a particular drug. Single cell genomics and spatial transcriptomics can be very influential in cancer. She gave an overview on her groups work on melanoma – specifically focusing on patients that have melanoma that is resistant to immunotherapies and how they used single-cell RNAseq to profile tumours in patients that have not responded well to immunotherapy – looking for common properties of malignant cells across different tumours.

Another cancer-focused presentation came from Zemin Zhang, from Peking University, China, who gave his talk virtually. He focused on exploring the complexity of the tumour microenvironment – specifically the identification of new sub-types, and how the tumour microenvironment can vary across different cancer types. His group compared different tumour types across the microenvironment, constructing a pan-cancer T-cell atlas across 21 different cancers from 316 patients, providing opportunities for personalised cancer therapy.

Single cell genomics has developed to such an extent that it’s now possible to have a high-resolution view on a whole developing animal. Cole Trapnell, from University of Washington, USA, described how these types of experiments can serve as references for developmental genetics. However, large-scale, single-cell RNAseq is expensive and he outlined an approach to reduce the costs associated with sequencing lots of single cells, using a tool called sci-Plex in combination with sci-RNAseq – a combinatorial indexing-based workflow. Using this approach enables the sequencing of millions of cells for lots of embryos in a single experiment. These type of approaches can be powerful allowing researchers to count the number of cells of each type in each embryo, compare them across different time points in development and in response to different perturbations, and examine their genomes; Cole went on to described how their whole embryo sci-Plex approach can lead to statistical developmental genetics – giving researchers the power to link molecular and cellular phenotypes to anatomical ones.

Staying with new technological approaches, Karen Leeat, from the Weitzman Institute, Israel, described how a multiplex proteomics imaging approach using MIBI-TOF (multiplex ion beam imaging by time of flight) allows sub-cellular resolution and means you can visualise proteins in situ. Her lab has used this method to explore how the lymph nodes are involved in cancer progression, by mapping lymph node architecture in people with melanoma. They identified particular immune signatures in non-metastatic Lymph nodes that are predictive of distant metastases within 5 years.

The community were excited to be back in person – meeting friends, colleagues and collaborators, networking and sharing the science. However, there was also an appreciation that hybrid format –the possibility of attending in person or virtually – offered more choice for delegates who cannot travel for a variety of reasons and is more inclusive. This year 92 delegates from countries in Africa, Asia and Latin America attended the conference, a much greater number than when the conference was held in person only.

We were delighted to receive excellent feedback from our delegates – whether attending in person or virtually – demonstrating the value of connecting multidisciplinary communities to global research.