The Human Cell Atlas (HCA) Consortium has released a blueprint for the international initiative’s efforts to create a comprehensive reference map of all human cells, a project that will form the basis for a deeper understanding of human health and for diagnosing, monitoring, and treating disease.
The consortium today also announced the impending release of gene expression profiles from the first one million immune cells collected under the HCA, toward an initial milestone of collecting at least 30 million cells representing several tissues and organs for the atlas’ first draft. These data, to be posted on an online repository by early November, will be freely available for researchers’ use.
* 1 million cells studied so far
* 30 million cells will be in phase 1
* long term goal is an atlas of 10 billion cells
The Human Cell Atlas (HCA) will be made up of comprehensive reference maps of all human cells — the fundamental units of life — as a basis for understanding fundamental human biological processes and diagnosing, monitoring, and treating disease. It will help scientists understand how genetic variants impact disease risk, define drug toxicities, discover better therapies, and advance regenerative medicine. A resource of such ambition and scale should be built in stages, increasing in size, breadth, and resolution as technologies develop and understanding deepens. We will therefore pursue Phase 1 as a suite of flagship projects in key tissues, systems, and organs. We will bring together experts in biology, medicine, genomics, technology development and computation (including data analysis, software engineering, and visualization). We will also need standardized experimental and computational methods that will allow us to compare diverse cell and tissue types — and samples across human communities — in consistent ways, ensuring that the resulting resource is truly global.
An extraordinary opportunity is emerging because of transformative advances in experimental and computational methods. Massively parallel single-cell genomics assays can now profile hundreds of thousands of cells. Technologies to profile DNA and proteins in single cells, as well as a combination of DNA, RNA, and proteins in the same cell, provide important additional layers of information. New spatial analysis techniques, including in situ assays, imaging approaches, spatial coding, and computational inference, allow high-resolution analysis of large tissues in two (2-D) or three (3-D) dimensions.
Computational algorithms have emerged to determine cell types, states, transitions, and locations from these new data, at increasing scale and resolution.
This first draft and the lessons learned in building it will serve as the basis for a comprehensive atlas of at least 10 billion cells, covering all tissues, organs, and systems — the necessary reference for future comparison and biological insight across disease areas, genetic diversity, environments, and ages. The cells will come from both healthy research participants and small cohorts of patients with relevant diseases, as these are critical to reflect on cells’ diversity. The cells will be studied using a broad range of techniques to capture both breadth and depth and will fully represent the world’s diversity.
They currently envision a Draft Atlas v1.0 that contains data from 30 million to 100 million profiled cells and their matching tissues, though the scale and scope may grow as measurement methods increase in throughput, robustness, and affordability.
The atlas should help researchers to compare healthy reference cells to diseased ones in the relevant tissues — and so facilitate the development of better drugs and more accurate predictions of unintended toxicity. The atlas could also aid regenerative medicine — the process of replacing, engineering or regenerating human cells, tissues or organs to establish normal function. Key diagnostic tests, such as the complete blood count — a routine blood screen that provides crude counts of white blood cells, red blood cells and so on — would become vastly more informative if cell types and states could be identified with much finer granularity. Such information could, for example, help to diagnose blood cancer, autoimmunity or infection before clinical symptoms appear.
Early studies are already showing tremendous potential in all these areas. New cell types have been found in the brai, gut, retina and immune system, and these discoveries have yielded new insight — into how the immune system11 functions, for example, and into the dynamics of tumor ecosystems. Yet, to take the next step — to build a human cell atlas that is truly useful — requires taking the long view and addressing various systemic and organizational challenges, as well as technical and scientific ones.
The first draft of the atlas will profile cells’ molecular and spatial characteristics, capturing only those cell types that occur above a pre-specified rarity — ones that make up more than 1% of a sample.
The first draft will focus on tissues, not whole organs. Extremely rare cells may be missed, and sample sizes may be too small to fully reveal the links between cellular characteristics and human diversity. In later phases, the atlas could take on entire organs, include small cohorts of people (say, 50–60) with diseases of interest, gather bigger sample sizes and provide greater power to associate molecular variation with the underlying genetic diversity. A similar step-wise strategy was deployed in the Human Genome Project; even a partially assembled genome proved immediately useful to researchers, and human genetic variation in health and disease was tackled over several years after the full genome was sequenced.