What do you see as the most important developments in your field in the past 10 years?
Single-cell mRNA sequencing has revolutionized many areas of biology and become ever more scalable and affordable during the past decade. It is now routine for papers to report the transcriptomes of tens or hundreds of thousands of cells from tissue samples. But it’s not just the transcriptome – we’ve also seen fantastic advances in multiomics (e.g. simultaneous assays of transcriptomes and epigenomic/proteomic features), which give a richer account of cell types/states. The next challenge is how to locate cell types within the complex tissue architectures of in vivo organs, and that’s where another ground-breaking advance comes in. Spatial transcriptomics encompasses several methods in which spatial information is retained in whole-transcriptome studies, allowing us to pinpoint cell types in tissues, and provides an integrated understanding of tissue anatomy. Spatial methods are increasing in power and resolution every year. Finally, the genomics community is increasingly benefitting from the development of deep-learning methods to recover meaningful biological information from the huge amounts of data we produce. To make this huge amount of data and the interpretations and knowledge from it available globally, we need to disseminate it via databases and web portals, and this is an ongoing challenge.
Tell us about one of your favourite published papers from your lab
One of my favourite papers was our single-cell mapping of the maternal–fetal interface in 2018 [Vento-Tormo, R. et al. (2018) Single-cell reconstruction of the early maternal–fetal interface in humans. Nature 563, 347–353. https://doi.org/10.1038/s41586-018-0698-6]. In this paper led by my amazing former postdoc Roser Vento-Tormo (who now runs her own lab at the Wellcome Sanger Institute), we wanted to understand the cellular interactions within and between the placenta and decidua that support early pregnancy. To do this we took samples from right across the whole placenta, and matched these with maternal uterine tissue (decidual) as well as maternal blood. The wide sampling across the placenta means that our paper was the first human organ mapped at scale. We included all cell lineages (stromal, epithelial, vascular, immune, etc.) to create a “cell type encyclopaedia”, and decoded the tissue architecture and spatial zonation of the decidua through integration with immunohistochemistry and multiplex smFISH to locate cells in the tissue. In this paper, we developed for the first time a method for prediction of cell–cell interactions (CellPhoneDB.org) based on receptor–ligand interactions with consideration of protein subunit stoichiometry. CellPhoneDB has been widely used by the genomics community ever since. In sum, this paper broke new ground experimentally and computationally, revealing many new insights into these tissues critical for development of human life yet relatively poorly understood. It was also our first foray into mapping of human cells (rather than mouse) and was soon followed by our papers on lung, heart, thymus, gut and immune systems.
What aspects of your life as a researcher do you most enjoy?
The things that I love the most are interacting with people and discussing data, results, interpretations and ideas. During some parts of the pandemic, when we couldn’t travel but could still meet in person, spending time with my research group members was a major benefit. And now that we are back to travelling, it is great to be able to interact with the international scientific community again, in person. This was much more difficult by Zoom, and I feel there is more energy and creativity in interactions in real life rather than virtual. At the same time, the pandemic did teach us how efficiently we can get things done in a virtual format, and that hybrid meetings are more eco-friendly and inclusive and can reach a huge audience worldwide.
What do you see as the main changes in the way researchers work in the past 10 years?
I believe that science massively benefits from teamwork and collaboration. I have seen this with my own work with the Human Cell Atlas (HCA), the international consortium that aims to map every cell type in the human body, which I co-founded with Aviv Regev in 2016 and co-lead to this day. The HCA now features over 2000 members around the world who all benefit from being in a network of dedicated, enthusiastic and creative research scientists. The success of consortia of course goes back to the Human Genome Project and later efforts such as the International Cancer Genome Project. On a smaller scale, within my lab and also the Cellular Genetics programme that I head in the Wellcome Sanger Institute I have striven to create a culture of collaboration. This synergy accelerates our scientific discoveries, as shown by how many of our papers are collaborative within the programme. I’ve also been delighted about what I perceive as a gradual evolution to a more equitable and diverse working culture. I truly believe that these changes lead to better science and faster progress.
What comes first: technique or biological question?
It is a combination of both: we want to develop and apply cutting-edge techniques (be they experimental or computational) to fundamental biological questions. Without the technique, the biology remains hidden; without the biological framework, the insights lack true transformative impact. The placenta/decidua paper mentioned above was a landmark both in the sense of techniques and biological insights, and our more recent work on the developing immune system [Suo, C., Dann, E. et al. (2022) Mapping the developing human immune system across organs. Science. https://doi.org/10.1126/science.abo0510] continues this trend. Here, in teamwork with the Haniffa and Clatworthy labs, we combined a comprehensive single-cell RNA sequencing atlas of the human developing immune system with antigen-receptor sequencing and spatial transcriptomics, to dissect the cross-gestation and cross-organ variability in immune cells. We discovered system-wide blood and immune cell development in unexpected locations like skin and gut, identified, characterized and functionally validated the properties of human B1 cell populations, and shed light on the origin of unconventional T cells. All of these important biological insights can only be revealed when cutting-edge techniques are integrated in a creative and innovative way to interrogate a biological framework.
Introduction to Sarah Teichmann's work
The Teichmann team is using single-cell approaches, so-called “cell atlas” technologies, combined with human genetics at the cellular level. They use cutting-edge techniques in the wet and dry lab and are applying these methodologies for further understanding of human health, development and disease. The team’s research focuses on four complementary study areas: transcriptional regulation and gene expression, single-cell genomics, immunology and protein complexes. Sarah Teichmann is co-founder and principal leader of the Human Cell Atlas international consortium, which aims to create comprehensive reference maps of all human cells to further understand health and disease.
Lab webpage: https://www.sanger.ac.uk/group/teichmann-group/
Sarah Teichmann will deliver the Opening Plenary Lecture (the 'IUBMB Claudina Rodrigues-Pousada Lecture') at the IUBMB–FEBS–PABMB Congress 2022 in Lisbon, Portugal on Saturday 9th July on ‘Human Cell Atlas: Mapping the human body one cell at a time’: https://2022congress.febs-iubmb-pabmb.org/
Top image of post: Developing B cells in prenatal gut – by Chenqu Suo, Sophie Pritchard and Nadav Yayon for the Wellcome Sanger Institute