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Major advances as scientists globally work towards first draft of Human Cell Atlas




Major advances have been announced in the quest to compile the first draft of the Human Cell Atlas - a map of all the cells in the body.

A collection of more than 40 peer-reviewed papers have been published in scientific journals, charting progress in our understanding in a host of areas from how the placenta and skeleton form to the maturation of the brain.

Human lung tissue. Picture: Nathan Richoz, University of Cambridge
Human lung tissue. Picture: Nathan Richoz, University of Cambridge

Contributed by researchers worldwide, the papers also provide essential tools and examples of how cell atlases can be built at scale.

They represent proof of principle that the Human Cell Atlas (HCA) consortium’s effort to capture all aspects of human diversity - in terms of genetics, geography, age and sex - at a cellular level can be achieved using cutting-edge technology.

Prof Sarah Teichmann, founding co-chair of the Human Cell Atlas, who is now based 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.

Prof Sarah Teichmann, founding co-chair of the Human Cell Atlas, now based at the Cambridge Stem Cell Institute
Prof Sarah Teichmann, founding co-chair of the Human Cell Atlas, now based at the Cambridge Stem Cell Institute

“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.”

The papers, published in Nature and other Nature portfolio journal, feature large-scale datasets, artificial intelligence algorithms and biomedical discoveries from HCA that are already transforming our understanding of the human body.

New gut and vascular cell states, lung responses to Covid-19 and the impact of genetic variation impacts on disease are among the findings reported.

Experimental and computational approaches in single-cell and spatial genomics are being used by the HCA consortium to create comprehensive reference maps of all human cells to help us better understand human health and the diagnosis, monitoring and treatment of disease.

The human small intestine. Picture: Grace Burgin, Noga Rogel & Moshe Biton, Klarman Cell Observatory, Broad Institute
The human small intestine. Picture: Grace Burgin, Noga Rogel & Moshe Biton, Klarman Cell Observatory, Broad Institute

The scale of the effort is quite staggering.

More than 3,600 HCA members from more 100 countries have worked together so far to profile more than 100 million cells from more than 10,000 people. There are teams of 18 biological networks in the HCA, each of which is focused on a particular organ, tissue or system.

The atlas will eventually feature billions of cells across all organs and tissues.

The new collection of studies illustrates 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 and machine learning-based methods.

Dr Aviv Regev, founding co-chair of the HCA, now at Genentech
Dr Aviv Regev, founding co-chair of the HCA, now at Genentech

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.”

A number of studies provide detailed analysis of specific tissues and organs that could help us understand disease.

Novel maps of human tissues during development have also been produced, including the first map of human skeletal development, revealing how the skeleton forms, casting light on the origins of arthritis and identifying cells involved in skeletal conditions.

Blood vessels in a human ileum sample. Picture: Ana-Maria Cujba, Catherine Tudor and Rasa Elmentaite
Blood vessels in a human ileum sample. Picture: Ana-Maria Cujba, Catherine Tudor and Rasa Elmentaite

Another study describes a multi omic atlas of the first trimester placenta. This offers insight into genetic programmes that control how the placenta develops and functions to provide nutrients and protection to the embryo.

Many diseases have their origins in human development so such studies give us fundamental knowledge that could aid the development of therapeutics.

There is also an article highlighting the importance of including samples from historically underrepresented human populations.

Prof 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.”

Skin organoid showing hair follicles with endothelial cells. Picture: Haniffa et al
Skin organoid showing hair follicles with endothelial cells. Picture: Haniffa et al

The HCA is also developing new ethical guidance on a broad range of issues in genomic science and making this advice available to scientists worldwide, as described in another article.

And new AI-powered methods to help us understand and classify cell types and search for cells in this vast map are described.

SCimilarity, for example, is the equivalent of a reverse image search for cells. It enables researchers to compare single-cell datasets to identify similar cell types in different tissues and contexts.

Other long-standing challenges tackled include how to classify cells into hierarchical groups based on their properties, a process known as cell annotation.

Dr Jeremy Farrar, chief scientist at the World Health Organisation, said: “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.”

More than 100 funding sources worldwide were used for the studies.




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