In recent years, technologies have been developed that now allow for interrogation of specific organs and the immune system down to the level of individual cells. The use of RNA sequencing, mass cytometry, and other techniques could generate better predictors of response to therapy, guide development of new therapeutics, and improve diagnoses.
Experts will discuss the promise and challenges of single-cell analysis during the Wednesday Clinical Science session Single Cell Analysis: Promises and Challenges, starting at 11:00 am.
Single-cell RNA sequencing (RNAseq) can provide an expression profile for individual cells in a variety of tissues. In one talk during the session, Nir Hacohen, PhD, Associate Professor of Medicine at Harvard Medical School and the director of Massachusetts General Hospital’s Center for Cancer Immunotherapy, will discuss a project aimed at defining dendritic cell and monocyte subtypes that are present in humans using RNAseq.
“The key goals are to be able to analyze immune responses in diseased tissues and blood in more depth than previously possible,” Dr. Hacohen said.
His group is also doing similar work on T cells and other cell types, hoping to reach that same depth of analysis.
“This will avoid the previous confounding of cell types in bulk expression studies, and lead to a better stratification of patients with nomination of novel therapeutic targets and predictors of response,” he said.
The new tools available today, such as RNAseq, allow a much deeper interrogation of autoimmune diseases than in the past.
“Biomarker discovery is central to the future of rheumatology, allowing us to diagnose better and to target therapies,” said Paul J. Utz, MD, Professor of Medicine at Stanford University in California.
Dr. Utz will discuss other new tools, such as mass cytometry, multiplexed ion beam imaging (MIBI)—which can measure protein levels on dozens of cells simultaneously as well as offering information on cell morphology and localization—and other related methods. These tools, he said, can be used to identify specific cell subsets and epigenetic pathways that may aid in diagnosis and therapeutic targeting.
Jill P. Buyon, MD, Director of the Division of Rheumatology at New York University’s Langone Medical Center, will also speak during the session and describe some of the details of the NIH-funded Accelerating Medicines Partnership (AMP) in Rheumatoid Arthritis and Lupus.
“One of AMP’s directives is to harness single-cell RNA sequencing to improve our understanding of the pathogenesis of lupus nephritis,” she said. “We want to leverage these discoveries to identify novel targets that may ultimately be responsive to therapy, and which may aid in predicting which patients will benefit from a specific approach. In this way we can move closer to personalized medicine.”
Dr. Buyon’s group is working on a project to use non-UV-exposed skin cells as a window to elucidate the mechanism of injury occurring in the kidney. Studies are underway to evaluate kidney and skin cell transcriptomes from patients with active lupus nephritis. Preliminary RNAseq data from skin cells suggests that correlations between the skin and kidney might in the future offer an opportunity to better gauge the effect of a therapy and avoid a second invasive kidney biopsy.
“Just thinking about the kidney as a target organ of systemic lupus erythematosus begs the question as to how other organs react to being bathed in cytokines and autoantibodies,” Dr. Buyon said.
She will also discuss some of the challenges inherent to single-cell analysis, such as ensuring the integrity and quality of the RNA, finding rare cell subpopulations, and making sure the results of sequencing are representative in useful ways. “There are a lot of pitfalls in doing this sort of work,” Dr. Buyon said.
In lupus nephritis and other diseases, the use of these single-cell technologies offers an array of avenues into diagnosis and treatment.
“Think of the power of applying this to other organ manifestations and other diseases,” Dr. Buyon said. “It would be rather incredible.”
CLINICAL SCIENCE TRACK
Single Cell Analysis: Promises and Challenges
11:00 am – 12:30 pm Wednesday