Single-cell transcriptome atlas of COVID-19 in primates arms scientists in the fight against SARS-CoV-2

In this guest blog post, Longqi Liu from Beijing Genomics Institute-Research and Miguel A. Esteban from the Guangzhou Institutes of Biomedicine and Health (Chinese Academy of Sciences), discuss their efforts in developing a better understanding of SARS-CoV-2 and how they utilized Single Cell Portal to make their research accessible to others.

The world has been rocked by the COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2. As a result, we — like our colleagues around the globe — would like to contribute our efforts towards better understanding this virus and its pathogenic mechanisms.

Since the initial outbreak, substantial progress has been made to uncover more about how this virus operates and the cell types that it targets, but many questions still remain. For example: what aspects of cells affect the virus’s ability to infect and destroy a cell? Does it attack cells in different species in different ways? Along with these questions, scientists are also working towards discovering new therapies and refining preventative approaches that can protect us until a permanent solution is found.

With the advent of single-cell profiling technologies, we are now able to unravel the transcriptomic and epigenetic features that determine the diversity of cell types within mammalian tissues (aka, their heterogeneity). Single-cell studies with human samples are already deciphering key aspects of COVID-19 and how the SARS-CoV-2 virus operates.

Despite this, in order to have a full and complete understanding of the virus, we need to collect data from other species, in particular those that are evolutionarily close to human. SARS-CoV-2, as we know, infected humans only after it had already jumped between several species. By looking at other species, we can see how they are infected by the virus, and how the viral response mechanisms are paralleled in humans. There is growing interest in using non-human primates, whether as models for studying COVID-19, or for testing vaccines and treatments. As such, we created a single-cell transcriptomic atlas of potentially disease-relevant organs in crab-eating macaque (cynomolgus monkey), as this would greatly help the ongoing work being done by the research community.

We did this in the context of a recently formed consortium in South East China, the South China Greater Bay Area Single Cell Consortium (SC-GBA-C). This consortium is a multicenter and multidisciplinary initiative that assembles scientists from the Guangdong region in China towards the goal of conducting work on single-cell technologies. The ultimate goal is not only to facilitate interactions between local scientists, but more importantly, to serve as a framework for scientific collaborations between China and the rest of the world.

With our brilliant colleagues working towards the same objective, we were able to quickly generate a very high-resolution atlas of nine monkey tissues at the single-cell level. This transcriptome atlas describes over 200,000 single cells, isolated from lung, kidney, brain, and various other tissues with potential relationship to COVID-19. We profiled the distribution of proteins that the coronavirus targets on cells in these tissues, and compared our findings with existing human datasets. Among other relevant observations, we noticed that these molecules were expressed differently, even within the same tissue.

By combining the transcriptome data of one of these organs (the kidney) with our single-cell chromatin accessibility data in the same organ, we were able to identify which genomic regulatory elements were of potential importance for the disease. The elements we identified were controlled by inflammatory cytokines such as interleukin 6 (IL6), which is a cytokine that has been implicated in COVID-19 pathogenesis. Knowing this, we hypothesized that increased IL6 levels (which normally occurs when a tissue is damaged), contributes to severe forms of COVID-19 by increasing the expression of virus-related targets in those tissues.

Our findings support work that is being done by other groups, who described an inflammatory loop driven by another group of cytokines — interferons — as a key event controlling the extent of SARS-CoV-2 entry into cells.

To make this data as accessible as possible to scientists studying this disease, our interactive database is now available through a dedicated page on Broad Institute’s Single Cell Portal. In addition to COVID-19, this dataset will be useful for making systematic comparisons of cell subtypes and disease vulnerabilities in monkey and human. We encourage you to look further at our dataset and find new useful correlations in your own data, in order to continue the fight against this pandemic.

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