Tu215 - A Deep Dive into a Wide Spectrum: Redefining Blood Cell States in Health and Disease

Pritha Sen; Jacquelyn Nestor; Alice Tirard; Nandini Samanta; Sidney Martin; John McGuire; Benjamin Arnold; Jessica Tantivit; Allen Steere; George Lauer; Maureen Leonard; Michael Mansour; Michelle Rengarajan; Sisi Sarkizova; Tom Eisenhaure; Nir Hacohen; Alexandra-Chloé Villani

Abstract Text: Blood is a window into human health and often used for disease diagnostics. It has been profiled by single-cell multi-omics technologies at greater depth than any other human tissue, but to-date these findings have not translated to clinical utility, possibly due to the focus on a different disease in every study. With the Human Cell Atlas moving towards providing a healthy reference map for all cell states in the human body, inevitable questions will arise about how this is altered in disease. To this end, we are building a blood single-cell multi-omics atlas encompassing over 5 million cells, incorporating healthy and 16 distinct immune-related disease states. Studying gene programs across diseases allowed us to understand how each cell state functions across different conditions and go beyond the current cell state definition that includes a set of unique markers it expresses. Trajectory analysis enables setting new boundaries to how we define a ‘healthy’ condition and studying in a new resolution how circulating immune cells change during disease. We identify shared dynamics of different cell states across disease conditions to better understand how the immune system works as a whole in the changing environment. This blood cell atlas provides a catalogue of the full spectrum of circulating PBMCs, enhancing healthy data atlases and fundamentally supporting future annotation of blood data in health and disease. Utilizing this compendium allows to answer a range of important questions in immunology with unprecedented resolution.