Host: Marko Jovanovic
Title: Deciphering regulatory networks from a single-cell vantage point: from intra-cellular gene expression towards inter-cellular signaling in tissue biology
Abstract: A journey into the dynamic regulatory networks that underpin immune cell differentiation and pathogenicity. First, I’ll discuss a study that combines transcriptional profiling at high temporal resolution with an innovative nanowire-based perturbation platform. This strategy enabled us to systematically derive and experimentally validate a dynamic differentiation model of Th17 cells, which are a pro-inflammatory T-cell subset implicated in autoimmune diseases. Interestingly, we find a mechanism that may be essential for maintaining the balance between Th17 and other T-helper cell subsets. Next, I'll discuss single-cell transcriptome profiling of Th17 cells isolated from tissues (central nervous system and lymph nodes) at the peak of experimental autoimmune encephalomyelitis or polarized in-vitro. The single-cell resolution enabled the characterization of divergent cell states adopted in vivo, and the analysis of co-variation patterns of gene expression, which led us to pinpoint novel regulators of pathogenicity, not just differentiation fate. Four of the new genes were functionally validated in knockout mice, and found to significantly affect disease susceptibility. This research has clarified that developing highly multiplexed and multi-omic assays for both isolated single cells and cells in their native tissue context will offer deeper insights into cellular decision-making and its resultant tissue physiology.