Journal article

Clonal multi-omics reveals Bcor as a negative regulator of emergency dendritic cell development

Luyi Tian, Sara Tomei, Jaring Schreuder, Tom S Weber, Daniela Amann-Zalcenstein, Dawn S Lin, Jessica Tran, Cindy Audiger, Mathew Chu, Andrew Jarratt, Tracy Willson, Adrienne Hilton, Ee Shan Pang, Timothy Patton, Madison Kelly, Shian Su, Quentin Gouil, Peter Diakumis, Melanie Bahlo, Toby Sargeant Show all

IMMUNITY | CELL PRESS | Published : 2021

Abstract

Despite advances in single-cell multi-omics, a single stem or progenitor cell can only be tested once. We developed clonal multi-omics, in which daughters of a clone act as surrogates of the founder, thereby allowing multiple independent assays per clone. With SIS-seq, clonal siblings in parallel "sister" assays are examined either for gene expression by RNA sequencing (RNA-seq) or for fate in culture. We identified, and then validated using CRISPR, genes that controlled fate bias for different dendritic cell (DC) subtypes. This included Bcor as a suppressor of plasmacytoid DC (pDC) and conventional DC type 2 (cDC2) numbers during Flt3 ligand-mediated emergency DC development. We then develo..

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Grants

Awarded by National Health and Medical Research Council, Australia


Funding Acknowledgements

We thank WEHI core facilities, including Bioservices, Centre for Dynamic Imaging, Flow cytometry, and Genomics; D. Hilton, M. Blewitt, S. Nutt, S. Taoudi, and J. Powell for critical reading of the manuscript; and J.-G. Zhang for Flt3L. This work was supported by grants from the National Health and Medical Research Council, Australia (GNT1062820, GNT1100033, GNT1101378, GNT1124812, and GNT1145184), and the Australia Research Council's special initiative Stem Cells Australia.