Human Cell Atlas Consortium Makes Major Progress in Understanding the Human Body

Researchers with the global Human Cell Atlas (HCA) consortium report significant progress in their quest for a better understanding of the cells of the human body in health and disease, with the publication today (20 November) of a Collection of more than 40 peer-reviewed papers in Nature and other Nature Portfolio journals.

The Collection highlights many of the large scale datasets, artificial intelligence algorithms and biomedical discoveries from HCA that are already transforming our understanding of the human body. Studies include revealing how the placenta and skeleton form, changes during brain maturation, new gut and vascular cell states, lung responses to COVID-19, investigating how genetic variation impacts on disease, and many more. 

The papers in the Collection were contributed by researchers worldwide. They provide essential tools and examples of how cell atlases can be built at large scale. Taken together, these studies provide a proof of principle for the HCA's bold endeavour to capture all aspects of human diversity, including genetic, geographic, age, and sex. 

The HCA is developing and using experimental and computational approaches in single-cell and spatial genomics to create comprehensive reference maps of all human cells-;the fundamental units of life-;as a basis for both understanding human health and diagnosing, monitoring, and treating disease. To date, more than 3,600 HCA members from over 100 countries have worked together to profile more than 100 million cells from over 10,000 people. Researchers are currently working to assemble a first draft Human Cell Atlas, which will eventually grow to include up to billions of cells across all organs and tissues. 

This Collection of studies in Nature Portfolio demonstrates major advances in three aspects of HCA's mission: mapping individual adult tissues or organs; mapping developing human tissues; and developing groundbreaking new analytical methods, including artificial intelligence / machine learning based methods. The researchers involved are members of the 18 Biological Networks of the HCA, each of which is focused on a particular organ, tissue, or system.

Professor Sarah Teichmann, founding co-Chair of the Human Cell Atlas, now at the Cambridge Stem Cell Institute, said: 'The Human Cell Atlas is a global initiative that is already transforming our understanding of human health. By creating a comprehensive reference map of the healthy human body-;a kind of 'Google Maps' for cell biology-;it establishes a benchmark for detecting and understanding the changes that underlie health and disease. This new level of insight into the specific genes, mechanisms and cell types within tissues is laying the groundwork for more precise diagnostics, innovative drug discovery and advanced regenerative medicine approaches.'

Dr. Aviv Regev, founding co-Chair of the HCA, now at Genentech, said: 'This is a pivotal moment for the HCA community, as we move towards achieving the first draft of the Human Cell Atlas. This collection of studies showcases the major advances from biology to AI achieved since the publication of the HCA White Paper in 2017 and that now deliver numerous biological and clinical insights. This large-scale, community-driven, globally representative and rigorously curated atlas will evolve continuously and remain accessible to all to advance our understanding of the human body in health and treatments for disease.'

Several studies in the Collection provide a detailed analysis of specific tissues and organs and reveal new biological discoveries important for understanding disease. For example, a cell atlas of the human gut from healthy and diseased tissue identified a gut cell type that may be involved in gut inflammation [Oliver at al.], providing a valuable resource for investigating and ultimately treating conditions such as ulcerative colitis and Crohn's disease. 

The new collection of papers also includes novel maps of human tissues during development. These include the first map of human skeletal development, revealing how the skeleton forms [To et al.], shedding light on the origins of arthritis, and identifying cells involved in skeletal conditions. An additional study describes a multi omic atlas of the first trimester placenta, including insight into genetic programmes that control how the placenta develops and functions to provide nutrients and protection to the embryo [Shu et al.]. These and other developmental biology studies in the Collection increase our fundamental understanding of healthy development in time and space, and provide blueprints and resources for creating therapeutics, since many diseases have their origin in human development.

An accompanying article highlights the importance of including samples from historically underrepresented human populations, and describes actions and principles aimed at promoting equitable science [Amit et al.]. 

Professor Partha Majumder of the John C Martin Centre for Liver Research and Innovation, India, and a member of the HCA Organising Committee member and Co-Chair of the HCA Equity Working Group, said: 'a key priority for HCA is to ensure a representation of the vast range of human diversity; genetic, cultural and geographical. HCA studies such as the Asian Immune Diversity Atlas and the analysis of distinctive histopathological differences in COVID-19 samples from Malawi demonstrate the remarkable power of large-scale international scientific collaboration.'

Another article illustrates HCA's role in developing new ethical guidance on a broad range of issues in genomic science and making this advice available to scientists worldwide [Kirby et al.].

Just as AI has revolutionised humans' ability to quickly process text, it is also now helping scientists to develop a deeper and more complete understanding of biology at the cellular level and beyond. The Collection introduces new AI methods to better understand and classify cell types and search for cells in this vast map. For example, SCimilarity [Heimberg et al.] enables researchers to compare single-cell datasets to identify similar cell types in different tissues and contexts, analogous to how "reverse image search" can search for photos. Other research teams tackled long-standing challenges such as classifying cells into hierarchical groups based on their properties, known as cell annotation [eg Ergan et al. and Fischer et al.] 

This landmark collection of papers from the international Human Cell Atlas community underscores the tremendous progress toward mapping every single kind of human cell and how they change as we grow up and age. The insights emerging from these discoveries are already reshaping our understanding of health and disease, paving the way for transformative health benefits that will impact lives worldwide."

Dr. Jeremy Farrar, Chief Scientist, World Health Organization

The individual studies in the Collection were funded by more than one hundred different funding sources worldwide*. The HCA also receives organisational support from the Chan Zuckerberg Initiative, Wellcome, the Klarman Family Foundation, the Helmsley Charitable Trust and others.