Maps of all human cells
The cell is the core unit of the human body—the key to understanding the biology of health and the ways in which molecular dysfunction leads to disease. Yet our characterization of the hundreds of types and subtypes of cells in the human body is limited, based partly on techniques that are outdated and classifications that do not always map neatly to each other. Genomics has offered a potentially systematic approach, but it has largely been applied in bulk to many cell types at once—masking critical differences between cells—and in isolation from other valuable sources of data.
Recent advances in single-cell genomic analysis of cells and tissues have put systematic, high-resolution and comprehensive reference maps of all human cells within reach – in other words, we might now be capable of building a human cell atlas to serve as a basis for both understanding human health and diagnosing, monitoring, and treating disease.
WHAT COULD A HUMAN CELL ATLAS BE?
At its core, a cell atlas would be a collection of cellular reference maps, charting each of the thousands of cell types in the human body and where they are found. It could be an extremely valuable resource to empower the global research community toward systematically studying the biological changes associated with different diseases, understanding where genes associated with disease are active in our bodies, analyzing the regulatory mechanisms that govern the production of different cell types, and sorting out how different cell types combine and work together to form tissues.
More specifically, a human cell atlas could:
- catalog all cell types (e.g, immune cells, brain cells) and sub-types in the human body,
- map cell types to their location within tissues and within the body,
- distinguish cell states (e.g., a naive immune cell that has not yet encountered a pathogen compared to the same immune cell type after it is activated by encountering a bacterium),
- capture the key characteristics of cells during transitions, such as activation or differentiation (e.g., from a stem cell), and
- trace the history of cells through a lineage, such as from a predecessor stem cell in bone marrow to a functional red blood cell.
A complete compendium of these features could serve as a basis for both understanding human health and disease, as well as diagnosing, monitoring, and treating disease.
WHAT IS THE ROLE OF AN INTERNATIONAL EFFORT?
Building a human cell atlas would require a collaboration across the international scientific community. Disparate fields of expertise in biology, medicine, genomics, technology development, and computation (including data analysis, software engineering, and visualization) would need to come together in a coherent, concerted way. Furthermore, an international effort must be able to compare across diverse cell types and tissue types in consistent ways, while studying samples from diverse human communities. This would likely require standardized methods and strategies.
WOULD IT BE WORTH IT?
Almost certainly. A human cell atlas would have immediate, tangible, and transformative benefits. For example, a cell atlas could:
- provide a reference map for comparing related cells, identifying new cell types, interpreting genetic variants, distinguishing disease from healthy states, and defining markers and signatures for pathology, cell sorting, and other measurements and tests,
- reformulate our fundamental definition of cell types, states and transitions,
- provide a direct view of human biology in vivo, removing the distorting aspects of cell culture, facilitating better comparison with current models and analysis of legacy data,
- identify the regulatory code that controls cell differentiation and cell–cell interactions, maintains cell state, and discover targets for therapeutic intervention, and
- drive the development of new technologies and advanced analysis techniques.
A human cell atlas would likely impact almost every aspect of biology and medicine, leading to a richer understanding of life's most fundamental units and principles.
WHAT MIGHT A CELL ATLAS PROJECT LOOK LIKE?
If an effort to build a human cell atlas is to be undertaken, we will need to understand exactly what a potential project could look like and address critical questions. Some of the important issues to be discussed include:
- What are all of the potential benefits of a human cell atlas?
- How to engage biological communities in specific areas?
- What should the scope of a human cell atlas be?
- From where and how should samples be sourced?
- How and where should samples be processed?
- Which technologies should be used, and which technologies must be developed further?
- What computational strategies will be most appropriate?
- How should activities toward a cell atlas be organized?
- What new biological communities need to be created?
- How should data be shared and disseminated?
- How can it be ensured that the global research community benefits from a human cell atlas?
In London on 13 and 14 October, 2016, we will begin to address these questions and more, with the goal of building a framework from which a human cell atlas could take shape.