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Single-cell proteo-genomic reference maps of the hematopoietic system enable the purification and massive profiling of precisely defined cell states

By Sergio H Triana, Dominik Vonficht, Lea Jopp-Saile, Simon Raffel, Raphael Lutz, Daniel R Leonce, Magdalena Antes, Pablo Hernandez-Malmierca, Diana Ordonez-Rueda, Beata Ramasz, Tobias Boch, Johann-Christoph Jann, Daniel Nowak, Wolf-Karsten Hofmann, Carsten Muller-Tidow, Daniel Huebschmann, Theodore Alexandrov, Vladimit Benes, Andreas Trumpp, Malte Paulsen, Lars Velten, Simon Haas

Posted 19 Mar 2021
bioRxiv DOI: 10.1101/2021.03.18.435922

Single-cell genomics has transformed our understanding of complex cellular systems. However, excessive costs and a lack of strategies for the purification of newly identified cell types impede their functional characterization and large-scale profiling. Here, we have generated high content single-cell proteo-genomic reference maps of human blood and bone marrow that quantitatively link the expression of up to 197 surface markers to cellular identities and biological processes across all hematopoietic cell types in healthy aging and leukemia. These reference maps enable the automatic design of cost-effective high-throughput cytometry schemes that outperform state-of-the-art approaches, accurately reflect complex topologies of cellular systems, and permit the purification of precisely defined cell states. The systematic integration of cytometry and proteo-genomic data enables the interpretation of functional capacities of such precisely mapped cell states at the single-cell level. Our study serves as an accessible resource and paves the way for a data-driven era in cytometry.

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