Watch our webinar with Harvard Medical Schools's Prof. Dr. Michael Brenner to learn more on the following:
Single-cell/single nucleus analyses including scRNA-seq, snATAC-seq, scTCR-seq, flow cytometry and CyTOF provide a new dimension in understanding human inflammatory diseases. They provide an unbiased approach to determine both the type and state of inflammatory cells and the tissue parenchymal cells and how they may interact in the pathologic state. We will examine all of the cell types and states found in the synovium in rheumatoid arthritis as a prototypical inflammatory disease. We will delineage (+20) the T cell types/states found and how they differ from what might have been expected based on past literature. This will include the major finding of a new T helper cell population that is implicated in B cell differentiation to antibody-producing cells that dominate among the CD4+ T cell states. Further, we will reveal the nature of the major tissue CD8+ T cell as granzyme K expressing, rather than the granzyme B expressing CD8+ T cells known in viral infections. B cell states and plasma cells will be enumerated with implications on the likely relevance of follicular and extrafollicular B cell differentiation. Inflammatory and non-inflammatory macrophages will be outlined, including our finding of a newly described super-activated macrophage state. Finally, the type and state of stromal fibroblasts that interact with the inflammatory leukocytes will be revealed as they directly mediate tissue damage. Besides the application of standard clustering algorithms, we will also employ recently described algorithms to assess neighbourhoods of cells that co-vary with implications for cell-cell interactions. We will then show how many of the interacting cells cooperate to produce the end-organ pathology in rheumatoid arthritis, many of which are shared across inflamed tissues.
The format is the following:
5 mins - introduction
20 mins - main discussion
20 min+ - Q&A