Creating the map of cells of the human body with support from the Chan Zuckerberg Initiative

The HCA project gathers scientists around the globe to work together on the fascinating idea of creating a map of cells that built the human body. Latest sequencing technologies are capable of analyzing one cell at a time and thousands of cells per experiment. Creating many such dataset for millions of cells across different tissues and organs will eventually enable drawing a high-resolution atlas of cellular composition. “A human cell atlas will help us to understand the complexity of our body with a resolution that could not have been imagined before” says Holger Heyn, member of the consortium and recipient of the CZI research grant. Most importantly, the atlas will serve as reference map for future work on illnesses, such as cancer or autoimmune diseases, to understand their origin and to identify targets for therapies.

In this initial phase of the HCA project, Dr. Heyn’s group now reaches out to identify the technologies that are most suitable to create such a comprehensive atlas of human cells. In the focus, single-cell RNA sequencing methods, which are at the forefront to inform about a cell’s phenotype. However, there are a plethora of conceptionally different methods and it remains elusive which protocols are most adequate to draw a tissue atlas. Before launching into large-scale production efforts, thus, merits comprehensive comparison of single-cell techniques. Within the framework of the CZI funded projects, Dr. Heyn will generate a comprehensive benchmark datasets to systematically evaluate techniques for their power to describe cell types and states.

The exercise includes 14 different methods with datasets produced at 18 research centers and companies. “For a fair comparison of techniques, we designed a unified sample at the CNAG-CRG that will now be shipped to the partnering laboratories. This complex sample includes different types of blood and colon cells helping us to simulate real scenarios within the HCA project”, explains Dr. Heyn and adds, “Beyond the initial selection of techniques, our reference sample will be available to benchmark future methods that might be even more powerful than currently available approaches”.

This project only got viable through last year’s discovery that single cells can be cryopreserved for single-cell sequencing applications, making it possible to store and transfer samples between laboratories. During the last year, Dr. Heyn’s group improved their protocols and produced more than a hundred vials of the cryopreserved HCA reference sample.

According to the Director of the CNAG-CRG, Dr. ivo Gut: “This project builds on the experience from the International Cancer Genome Consortium, where we lead a large-scale benchmarking study of cancer genome sequencing and somatic mutation calling. This experience taught us the importance of laying a solid foundation for an ambitious multi-year project. We are delighted that the CZI shares our view and is supporting us.”

There are 85 collaborative projects being recommended for funding in response to an open Request for Applications issued by CZI in July 2017. Funding is being awarded to 83 principal investigators at 53 institutions, and in nine countries spanning four continents. Detailed information on each project is available at this link [+info].