Dec 21, 2020

Year in review: Looking back at top research publications from 2020

Jeanene Swanson

Even though it’s been a challenging year, we at 10x Genomics are proud of and inspired by all the great research that’s been carried on or initiated in spite of the COVID-19 pandemic. In particular, we’re proud—and humbled—to present a handful of some of the most inspiring research published this year using 10x Genomics single cell technologies.

In this blog post, we round up some of the most intriguing published research that makes use of 10x Genomics single cell technologies, ranging from neuroscience to oncology and immunology. Let’s take a look back at the discoveries made this year and how leading scientists, with the help of 10x Genomics single cell tools, are advancing our knowledge of biology across human health and disease.

Neuroscience: Peeling back layers of complexity in Alzheimer’s disease

In a paper published in Cell titled, Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer’s Disease, scientists led by top Alzheimer’s disease (AD) researchers Drs. Bart de Strooper and Mark Fiers at VIB-KU Leuven Center for Brain & Disease Research in Belgium leveraged spatial gene expression approaches to study the molecular pathology of this degenerative brain disease, revealing key molecular changes and cellular interactions within a network of glial cells in the vicinity of amyloid plaques.

“Single cell tools are ushering in a new era of discovery in neuroscience,” says Kelly Miller, PhD, Senior Manager, Neuroscience Marketing at 10x Genomics. “Using spatial transcriptomics at the level of single cells—which has never been done before on AD tissue—adds new layers of insight into the location of genetic alterations in specific brain cell types associated with pathological features of disease.”

In the study, the authors employed a combination of spatial transcriptomics, complemented by in situ sequencing for validation and to confirm cell-specific gene localization, to interrogate mouse and human brain in the context of non-neuronal cells surrounding AD plaques. Their results revealed multicellular gene co-expression networks in AD, two of which are induced by accumulating amyloid plaques. A plaque-induced gene (PIG) network mainly involved microglia and astroglia while an oligodendrocyte gene (OLIG) network showed high expression of myelination genes.

For more information on this study, read the 10x Genomics blog post.

Oncology: Drawing a high-resolution picture of the tumor microenvironment in skin cancer

In other research also published in Cell, “Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma,” Dr. Paul Khavari’s group at Stanford University integrated single cell and spatial transcriptomics to create an atlas of cell types and states in squamous cell carcinoma and characterize the spatial niche in which these cells reside. The team was able to identify physical patterns of colocalization and exclusion of cell populations within the tumor microenvironment and adjacent tissue, and define the ligand-receptor pairs mediating cellular crosstalk between specific cell types. By cataloguing these patterns across the tissue section, the researchers were able to define tumor and immune cell dynamics within the tumor, at the leading edge, and in the adjacent normal tissue. They identified a subpopulation of tumor-specific keratinocytes (TSK) localized to the leading edge of the tumor, which acts as a hub for intercellular communication and a potential driver of metastasis.

Coupling single cell and spatial transcriptomics is not just additive—it transforms our ability to not only identify the diverse cell populations in the tumor ecosystem, but discover the fundamental spatial constraints underlying cellular crosstalk, functional plasticity, and, ultimately, cancer progression.

“Mulitomic single cell approaches are relatively new, and this study drives home the power of being able to localize the changes going on in the tumor microenvironment on a cell-by-cell basis, in both normal and diseased tissue,” says Abbey Cutchin, Manager, Oncology Marketing at 10x Genomics.

Immunology: Deciphering the relationship between severity and prognosis in treating COVID-19 infection

Finally, in a paper published in Cell called “Multi-Omics Resolves a Sharp Disease-State Shift between Mild and Moderate COVID-19,” scientists led by Dr. Yapeng Su at the Institute for Systems Biology in Seattle implemented a multiomics approach, incorporating 10x Genomics Single Cell Immune Profiling to study the disease immunology of mild to moderate COVID-19 infection. Taking blood during the first week of infection from 139 COVID-19 patients representing all levels of disease severity, they integrated clinical data, immune cell classes, and plasma multiomic profiles, finding that there is a major immunological shift between mild and moderate infection (as compared to moderate and severe cases). This includes an increase in inflammation and a decrease in blood nutrients, as well as the development of novel peripheral immune cell subpopulations that become more prominent as the severity of disease increases, including two distinct CD4+ T-cell subpopulations.

This study suggests that treatments will be most effective during a state of moderate disease severity.

“A more complete understanding of the immune responses that correlate with COVID-19 disease severity is essential to understanding how to treat this disease more effectively,” says Brian Fritz, PhD, Director, Segment Marketing at 10x Genomics. “With single cell tools, we can study the fundamental cellular biology of disease, which will in turn lead to better prognosis and patient stratification, and potentially novel treatment paths. Studying the response to treatment at a single cell level also gives us critically enhanced resolution for understanding how immune and other cell types respond to different therapeutic approaches in affected individuals.”

While these publications represent only a small fraction of the excellent research published this year using 10x Genomics single cell tools, it is our hope that they give you some idea of the power of single cell approaches to advance our understanding of what’s behind complex biological processes and disease progression. Whether for single cell transcriptomic analysis, immune cell mapping, or spatial gene expression studies, single cell analyses can be applied across many disciplines to make discoveries that drive translational research forward. We can’t wait to see what next year brings!