Researchers around the globe are still struggling to understand the basic biology of COVID-19 infection, including how it works in the body and how to most effectively combat it. To aid them in their efforts under the weight of the ongoing pandemic, single-cell research tool company 10x Genomics Inc. has launched an updated version of its Chromium Single Cell Immune Profiling product.

10x Genomics has been key in providing tools for major research projects, most prominently the Human Cell Atlas that seeks to map all the cell types in the body and to better understand their function. Its products have been behind more than 1,000 research papers and are in use at 97 out of the top 100 global research institutions and 19 of the top 20 global pharmaceutical companies. Since its IPO last September, which was a top performer for 2019, the Pleasanton, Calif.-based company has managed to achieve a roughly $8.5 billion market cap.

More and deeper

The updated product can detect “up to 60% more genes per cell depending on the cell type” 10x Genomics co-founder and CSO Ben Hindson told BioWorld. “That's the kind of boost that customers will be able to see this new version; it’s so much more sensitive. You're able to see more genes – you can see more potentially at the equivalent or lower sequencing costs as well.

“You can see more information per cell and you can get deeper, if you want to look deeper into each cell across thousands, tens of thousands, even millions of cells, and then gives you that flexibility, depending on what you want to look for,” he added.

With the existing Chromium Single Cell V(D)J Solution, researchers can also expect to see up to 40% more molecules per cell. The new product version will work in tandem with its recently launched Targeted Gene Expression Solution that was just launched in May. That offers immunology and cancer panels that enable a close focus on selected genes, which decreases costs and can enable a more in-depth examination into, say, 1,000 genes that are of interest, depending on the panel.

Version two of the Chromium Single Cell Immune Profiling can be used to characterize adaptive and innate immune cell diversity; identify and characterize rare cell types and biomarkers; analyze the tissue microenvironment, disease progression and drug immune response; perform large-scale antibody and T cell receptor discovery for novel antigens; and to characterize immune responses to infection by measuring clonal expansions and immune cell phenotypes.

These capabilities are likely to prove widely useful across many fields including oncology, autoimmunity and infectious diseases. But, of course, COVID-19 is the top research priority for many as researchers look for useful treatment targets and physicians struggle to employ the best existing tools to treat the disease.

The role of rare immune cells is a hot research topic currently independent of the pandemic, but it also could prove key in understanding who is most vulnerable to severe COVID-19 infection.

Rare cell discovery

“[Cellular] diversity is obviously key, especially when you're trying to find rare cells and low expressing genes,” said Hindson. “This way of interrogating and mapping the immune system is really at the beginning, and tools like this can provide the fundamental resolution that you need to get that understanding much faster. We believe this is a huge opportunity, a huge upgrade that should make the information even more powerful than our first version.”

“Biomarker discovery is also related,” he continued. “Fractions of cells only may be there, some of the interesting cells may be there in only a few percent abundance. We are seeing this in the COVID research, these rare cells can actually play a hugely important role in the ecosystem. So, finding those cells and then tracking and tracing them where they are – and what they're doing at different points in time and in different geographies in a given tissue is also very interesting.”

He pointed specifically to a particular Stanford University preprint paper from March examining lung cells that came out of the Human Cell Atlas work. The researchers found 41 out of 45 previously known cell types in normal lung tissue, with the missing ones being prominent only in the context of lung disease. They also identified 14 new cell types that had previously been undetected and undescribed.

The novel cell populations were found across the four lung tissue types and were molecularly distinct from known cell types. “These include an abundant alveolar epithelial cell type (AT2-s) intermingled with the classical cell types (AT1 and AT2), which may have stem cell function; two molecularly distinct capillary cell types; new fibroblast subtypes including alveolar and adventitial fibroblasts and ones we call ‘fibromyocytes’ that share markers with airway smooth muscle; and three new resident dendritic cell populations,” the paper noted. “Each of the newly identified molecular cell types must be thoroughly characterized to define their structures, functions, stabilities, development and role in disease.”

The hope is that this sort of research can help to provide the basis for elucidating the mechanisms of how COVID-19 infection works in the body, thereby rendering the most effective treatment targets visible and potentially druggable.

There have already been more than a dozen COVID-19-related, peer-reviewed papers that were based on the prior version of the 10x Genomics Chromium Single Cell Immune Profiling product. These include efforts to better understand which cells in organs and tissues become infected; how the immune system responds to infection across patients with varying disease severity; and the ways neutralizing antibodies can be used to block virus entry into host cells.

“With the number of coronavirus cases expected to reach 100,000 a day in the U.S. alone, it is critical that we get the right products into the hands of scientists as soon as possible,” said Hindson. “Our new product adds a powerful tool to our customers’ arsenal for combating COVID-19 and other deadly diseases, and is a testimony to our very rich product pipeline.”

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