More than 100 members of the Geisel School of Medicine’s research community gathered recently in Auditorium E at Dartmouth Hitchcock Medical Center to learn about some of the most advanced tools and technologies available today within the areas of single cell and spatial transcriptomics.
Hosted by the Center for Quantitative Biology (CQB) at Geisel, the daylong symposium featured presentations from eight Dartmouth Cancer Center investigators (see the list of investigators and their projects below) who showcased their use of these technologies in working to drive new discoveries in cancer biology, immunology, and autoimmunity.
“There are a lot of really exciting, high-impact projects going on that we support through our facilities,” says Fred Kolling, PhD, who directs both the Cancer Center Genomics Shared Resource and Single Cell Genomics Core within the CQB and helped organize the symposium. “Our goal was to bring folks together who are interested in doing this type of work, give them some ideas on the different tools they can apply to their research, and provide networking opportunities.”
Established in 2019 as an NIH-funded Center for Biomedical Research Excellence (COBRE), the CQB entered its second 5-year grant phase last summer and continues to provide expertise and resources in single cell and spatial genomics and genomic data science, as well as research administration and mentoring, to investigators and their teams.
“Single-cell genomics is a rapidly evolving field—having a dedicated center with resources behind it gives us the ability to quickly bring on the latest technologies, test them, and determine which ones can best meet the needs of our investigators,” says Kolling, who notes that since 2019 the CQB has run over 900 single cell samples for 60 different labs both in and outside of Dartmouth.
When asked to describe the advantage of being able to generate single-cell genomics data over more traditional approaches, Kolling employs a commonly used analogy. “It’s like the difference between being able to examine the individual pieces of fruit in a fruit salad and those same pieces of fruit after they’ve been blended together to make a fruit smoothie,” he explains.
“Similarly, if you prepare a normal bulk analysis of a blood sample, which may contain dozens of immune cell types, you’re going to get an average measurement of all the different types of cells that are in that sample. That analysis can offer some useful information, but to do precision medicine you need to know the type of cell that you’re targeting to develop the treatment. In essence, that’s what single cell does.”
Spatial transcriptomics takes that capability to another level, says Kolling, allowing investigators to do single-cell sequencing in the context of a three-dimensional tissue such as a tumor biopsy.
“One of the most exciting new tools we have to do that with is the Xenium platform from 10x Genomics, which lets us look at where each cell is located within the tissue, in relation to other cells and with much more detail,” he explains. “For example, using traditional histology, researchers could look at maybe 5 or fewer features in a tissue sample. We’re at the point now where we can look at over 5,000 features in the context of the tissue, and then, importantly, provide a framework for the downstream analysis and interpretation of that data.”
Based on the strong attendance and positive feedback received from symposium participants, Kolling and his colleagues are planning to offer a similar event next year. “It’s not easy to get eight faculty members in the same place for a full day,” he says, “but this event demonstrated that everyone was excited to get together, network with their colleagues, and learn about the cutting-edge technologies we’re making available to researchers here at Dartmouth. That was really neat to see.”
| Symposium Presenters | Projects |
| Aaron McKenna, PhD, assistant professor of molecular and systems biology | Dissecting treatment resistance in cancer with single-cell lineage tracing |
| Mary Jo Turk, PhD, professor of microbiology and immunology | Single cell RNA sequencing to define tissue-resident memory T cells in mice and patients with melanoma |
| Alos Diallo, PhD | Deciphering the spatial dynamics of cancer associated fibroblasts and CD8+ T cells in colorectal cancer metastasis using spatial and single-cell transcriptomics |
| Sladjana Skopelja-Gardner, PhD, assistant professor of microbiology and immunology |
Unraveling neutrophil roles in lupus nephritis: insights from spatial, single-cell, and epigenetic analyses |
| Lucas Salas, MD, MPH, PhD, assistant professor of epidemiology | Dissecting the cellular and epigenetic landscape of clear cell renal cell carcinoma through paired snRNA/ATAC-seq analysis |
| Pamela Rosatao, PhD, assistant professor of microbiology and immunology | Unraveling T cell identity and function in the brain |
| Edward Usherwood, PhD, professor of microbiology and immunology | Spatial and single-cell transcriptomics to track changes induced by T cell immunotherapy against melanoma |
| Claudia Jakubzick, PhD, professor of microbiology and immunology |
Single-cell sequencing and spatial profiling of macrophages |
To watch a selection of the symposium presentations via Zoom, go to: https://sites.dartmouth.edu/cqb/symposium-videos/
