Abstract
Single-cell genomics technology has transformed our understanding of complex cellular systems. However, excessive cost 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 main 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 functional capacities of precisely mapped cell states to be measured at the single-cell level. Our study serves as an accessible resource and paves the way for a data-driven era in cytometry.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Nature Immunology |
| Vol/bind | 22 |
| Udgave nummer | 12 |
| Sider (fra-til) | 1577-1615 |
| Antal sider | 39 |
| ISSN | 1529-2908 |
| DOI | |
| Status | Udgivet - 2021 |
Bibliografisk note
Funding Information:We thank V. Lopez-Salmeron, V. Ramani, E. Kowalczyk and W. Keilholz from BD Biosciences/Multiomics for providing oligo-labeled antibodies and for their support in the implementation of the Rhapsody platform. We would like to thank members of the Haas, Velten, Trumpp and Steinmetz laboratories for helpful discussions. Moreover, we thank members of the DKFZ flow cytometry and the EMBL genomics core facility for support. This work was supported financially by the Emerson foundation grant 643577 (to L.V.), grant PID2019-108082GA-I00 from the Spanish Ministry of Science, Innovation and Universities (MCIU/AEI/FEDER, UE), the German Bundesministerium für Bildung und Forschung (BMBF) through the Juniorverbund in der Systemmedizin ‘LeukoSyStem’ (FKZ 01ZX1911D to L.V., S.H. and S.R.), SFB873, FOR2674 and FOR2033 funded by the Deutsche Forschungsgemeinschaft (DFG), the SyTASC consortium (Deutsche Krebshilfe), The Darwin Trust of Edinburgh (to S.T.), the ERC Consolidator Grant METACELL (773089) (to T.A.), the Dietmar Hopp Foundation (all to A.T.) and the José Carreras Foundation for Leukemia Research (grant no. DCJLS 20R/2017 to L.V., A.T. and S.H.). L.V. acknowledges the support of the Spanish Ministry of Science and Innovation to the EMBL partnership, the Centro de Excelencia Severo Ochoa and ‘the CERCA Programme/Generalitat de Catalunya. D.N. is an endowed professor of the Deutsche José 641Carreras Leukämie Stiftung (DJCLS H 03/01). Contributions by D.N., J.-C.J., W.-K.H. and T.B. were supported by the Gutermuth Foundation, the H.W. & J. Hector fund, Baden-Württemberg. Figure 1a and Supplementary Note Fig. 3f were created at BioRender.com.
Publisher Copyright:
© 2021, The Author(s).