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V. Michael Holers, MD
University of Colorado
Denver, CO, United States
Disclosure(s): No financial relationships with ineligible companies to disclose
Until now, functionally relevant stromal cell populations have proven difficult to define, characterize and study in health and disease. Consequently, there are no approved drugs that specifically target stromal cells in human diseases. In contrast the identification of leucocyte subsets with non-overlapping effector functions provided a molecular framework for the development of targeted therapies that have demonstrated spectacular success in immune-mediated inflammatory diseases (IMIDs). Two revolutions have occurred to bring our understanding of stomal cell populations to the same level that has been achieved for leucocytes. The first was minimally invasive biopsy procedures that allow resident tissue cells to be obtained, often over time and the second was the advent of single cell sequencing that allow stromal cells to be characterized and their location within tissues mapped. Both have been essential to the foundation of the Human Cell Atlas (HCA) [1]
Unlike haematological diseases where the gene (haemoglobin), cell (red blood cell) and clinical features (anaemia) map well onto each other, the cellular basis for most inflammatory diseases remains enigmatic. The HCA was established to construct a map of the different cell types involved in forming human organs using single cell analysis with spatial analysis to locate their position in tissue. Its aim is to provide life scientists with a “medical periodic table” analogous to the “chemical periodic table”. Its implications for experimental medicine are what I will describe in this lecture. Using the principles of the HCA in an Arthritis Therapy Acceleration Programme (A-TAP) we have assessed how the cellular composition of tissue is affected following treatment in different IMIDs. This therapeutic cell atlas can be used to instruct and power experimental medicine studies where a common cell-based marker is used in Bayesian driven basket trials across a range of IMIDs [2].
References
1. https://www.humancellatlas.org/
2. Immune-mediated inflammation across disease boundaries: breaking down research silos. Buckley CD, Chernajovsky L, Chernajovsky Y, Modis LK, O'Neill LA, Brown D, Connor R, Coutts D, Waterman EA, Tak PP. Nat Immunol. 2021 Nov;22(11):1344-1348. doi: 10.1038/s41590-021-01044-7. PMID: 34675389
Speaker: Christopher Buckley, MD, PhD – University of Oxford
