Today, Nature and other Nature Portfolio journals published a collection of more than 40 peer-reviewed papers marking a milestone toward researchers' understanding of the human body in health and disease and the development of the first draft of the Human Cell Atlas (HCA) . The Human Cell Atlas is an international community whose mission is to align groups engaged in creating comprehensive reference maps of all human cells — the fundamental units of life — as a basis for understanding human health and for diagnosing, monitoring, and treating disease. The Chan Zuckerberg Initiative (CZI) is one of the HCA's first and largest funders and provided support for a third of the papers included in this landmark release. The research papers cover an impressive variety of tissues, cell types, and organs, such as the brain, immune system, thymus, and endometrium. These papers advance scientific research by introducing novel methods and frameworks for improving the analysis, integration, and visualization of complex, high-dimensional single-cell and multi-omics datasets, enabling more accurate cell type identification, spatial mapping, and understanding of cellular heterogeneity across various biological contexts and diseases.
"The Human Cell Atlas was one of the Chan Zuckerberg Initiative's first big bets in supporting science, and I'm so pleased to see these landmark papers that share the work with the larger scientific community," said Stephen Quake, Head of Science at CZI. "Beyond the individual scientific discoveries reported in the collection, it is also worth emphasizing the value of the shared data for science, especially in the age of AI where enormous amounts of data can be better analyzed to further accelerate research and aid in CZI's mission to cure, prevent, or manage all diseases by the end of the century."
Dedicated to supporting basic science and technology, CZI began funding projects that would contribute to the HCA in 2017 as some of CZI's first grants ever awarded. The initial 38 funded projects, called the Pilot Projects for the Human Cell Atlas , focused on establishing benchmarks, methods, and protocols that would lay the groundwork for future HCA projects and establish methods and protocols to align this global effort. Many of the initial funded projects or work that builds off of these efforts are highlighted in this paper collection.
For example, recognizing the need for a globally representative cell atlas, Dr. Harikrishna Nakshatri and colleagues at Indiana University began their CZI Seed Networks project, " Single cell mapping of the normal breast of ethnically diverse populations ," in 2019. Their findings , which are included in Nature's collection, offer a comprehensive chromatin accessibility and gene expression atlas of human breast tissues, using samples from 92 healthy donors of different genetic backgrounds. Using single-cell technologies, Dr. Nakshatri's team identified all cell types commonly found in breast tissue, including two cell types, the luminal adaptive secretory cells and fibroblasts, which demonstrated genetic ancestry-dependent variability among those of Indigenous American and African ancestry. This finding not only contributes much-needed data from previously understudied populations to the HCA, but also provides new insights into how genetic ancestry can influence disease susceptibility, treatment responses, and other health-related outcomes. View the data in Chan Zuckerberg CELL by GENE .
"This collection of papers is a testament to the global grassroots federation of researchers that are motivated to discover more about our cells and how they function," said Jonah Cool, Senior Science Program Officer, Cell Science at CZI. "As an early supporter of the Human Cell Atlas, the Chan Zuckerberg Initiative has funded researchers to generate data and developed computational tools and methods to explore these data. It's gratifying to see the results of the scientific community's collective work, including CZI's efforts to support researchers to contribute ancestrally diverse tissue samples, with the aim of creating a more globally representative resource to understand disease."
Given the immense generation of data from the HCA and other research efforts, CZI developed the software tool Chan Zuckerberg CELL by GENE (CZ CELLxGENE) to provide biologists around the world with access to the largest curated corpus of standardized single-cell datasets, with nearly 100 million cells and growing. CZ CELLxGENE allows scientists to explore and visualize high-dimensional single-cell datasets — such as those within the HCA — to more quickly surface important information that could lead to discoveries in treating disease.
Single-cell datasets generated by efforts like the HCA, and made available via software tools like CZ CELLxGENE, are opening the door to a new era of AI-driven scientific research. These datasets can be used to train AI models that can unlock new insights about human health and disease. CZI is creating virtual cell models that will allow scientists to predict what causes certain cells to go haywire when people become sick and what it takes for cells to become healthy again. Building off the foundation of data generation, and software development, we hope these models continue to deepen our understanding of human biology at a molecular level — bringing scientists closer to curing, preventing or managing all diseases by the end of this century.
About the Chan Zuckerberg Initiative
