Sheng Zhong, PhD
Professor of Bioengineering
Incentivizing More Representative Research
Supporting Tissue Diversity for the Human Cell Atlas
The field of genomics overall has fallen short of generating and sharing data that is representative of the global population, leading scientists all over the world to call for more genetic diversity in studies and research. For example, our knowledge about some diseases is biased toward the mechanisms and genes that underlie these conditions primarily in populations of European ancestry. We also know that studies based on a narrow slice of ancestral background are often not generalizable to all people. Extending this information and understanding to include individuals from across the globe strengthens our overall understanding of the pathways and genes associated with diseases in different populations.
Researchers worldwide are working together to create a common reference map of all human cells that will allow us to better understand and treat disease: the Human Cell Atlas (HCA).
Dr Sheng Zhong, Professor in the Department of Bioengineering and Dr. Zhen Bouman Chen, Associate Professor at the Beckman Institute at the City of Hope have received support from the Chan Zuckerberg Institute to increase tissue diversity from understudied racial, ethnic, and ancestral populations in Human Cell Atlas projects. To expand the racial diversity of this atlas, Drs. Zhong and Bouman Chen will include samples from Black and Latinx donors, which will help to clarify how cardiovascular disease manifests differently among various populations.
Their HCA project aims to build an endothelial cell atlas in space and time by mapping the transcriptomes of endothelial cells from several tissues from donors of different ages and developing cutting-edge computational tools.
Members of the Zhong lab have shown that human-genome produced RNA is present on the surface of human cells, suggesting a more expanded role for RNA in cell-to-cell and cell-to-environment interactions than previously thought. This new type of membrane-associated extracellular RNA (maxRNA) is found in human cells that are not undergoing cell death, shedding light on the contribution of nucleic acids—particularly RNA—to cell surface functions. The maxRNAs and the molecular technologies developed to inspect the cell surface to detect them, are detailed in a paper in Genome Biology published Sept. 10, 2020.
Members of the Zhong lab have also developed a technology capable of revealing the protein-protein interaction (PPIs) among thousands of proteins, in a single experiment. The tool, called PROPER-seq (protein-protein interaction sequencing), allows researchers to map the PPI network from their cells of interest within several weeks, without any specialized resources such as antibodies or premade gene libraries. The researchers describe this technology in Molecular Cell on August 3, 2021. In this work, they applied PROPER-seq on human embryonic kidney cells, T lymphocytes, and endothelial cells, and identified 210,518 PPIs involving 8,635 proteins (Figure 2).
Applying these cutting edge-techniques to an inclusive database of donor samples will improve the value and functionality of the HCA to more researchers globally, and inform a wider array of disease states for patients across the globe.