题 目: Single-cell proteomic and transcriptomic analysis of macrophage heterogeneity
报告人: Dr. Nikolai Slavov
Allen Distinguished Investigator
Bioengineering Department and Barnett Institute, Northeastern University
时 间: 10月12日（周一）9:00-10:00
地 点: Online (Zoom会议)
会议 ID：627 9242 4126
主持人: Lucas Carey
The fate and physiology of individual cells are controlled by proteins. Yet, our ability to quantitatively analyze proteins in single cells has remained limited. To overcome this barrier, we developed SCoPE2. It substantially increases quantitative accuracy and throughput while lowering cost and hands-on time by introducing automated and miniaturized sample preparation. These advances enabled us to analyze the emergence of cellular heterogeneity as homogeneous monocytes differentiated into macrophage-like cells in the absence of polarizing cytokines. SCoPE2 quantified over 2,700 proteins in 1,018 single monocytes and macrophages in ten days of instrument time, and the quantified proteins allowed us to discern single cells by cell type. Furthermore, the data uncovered a continuous gradient of proteome states for the macrophage-like cells, suggesting that macrophage heterogeneity may emerge even in the absence of polarizing cytokines. Parallel measurements of transcripts by 10x Genomics scRNA-seq suggest that SCoPE2 samples 20-fold more protein copies than RNA copies per gene, thus supporting quantification with improved count statistics. Joint analysis of the data suggested the feasibility of inferring transcriptional and post-transcriptional regulation. Our methodology lays the foundation for automated and quantitative single-cell analysis of proteins by mass-spectrometry.
Nikolai Slavov’s group seeks principles in the coordination among protein synthesis, metabolism, cell growth and differentiation. The Slavov group has pioneered high-throughput mass-spectrometry methods for quantifying proteins in single cells and is developing new computational methods for analyzing and understanding single-cell proteomics and multimodal data. The group obtained direct evidence for a new regulatory mechanism of protein synthesis (ribosome specialization) and continues to drive research in this emerging field supported by the NIH Director’s New Innovator Award. Nikolai Slavov studied biology and physics at MIT before completing a dissertation at Princeton University (Botstein laboratory) with research focused on the coordination among metabolism, growth and gene expression. Dr. Slavov then returned to MIT (van Oudenaarden laboratory) for post-doctoral research that characterized trade-offs of aerobic glycolysis. Professor Slavov actively organizes community initiatives, such as the annual single-cell proteomics conference (single-cell.net/), which is a highly interactive and interdisciplinary meeting. He also participates and contributes to organizing other leading conferences, including NeurIPS and HUPO.