Portal de Periódicos da CAPES

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

2021; Cell Press; Volume: 54; Issue: 6 Linguagem: Inglês

10.1016/j.immuni.2021.03.012

1097-4180

Luyi Tian, Sara Tomei, Jaring Schreuder, Tom Weber, Daniela Amann‐Zalcenstein, Dawn Lin, Jessica Tran, Cindy Audiger, Mathew Chu, Andrew Jarratt, Tracy A. Willson, Adrienne A. Hilton, Ee Shan Pang, Timothy Patton, Madison J. Kelly, Shian Su, Quentin Gouil, Peter Diakumis, Melanie Bahlo, Tobias Sargeant, Lev M. Kats, Philip D. Hodgkin, Meredith O’Keeffe, Ashley P. Ng, Matthew E. Ritchie, Shalin H. Naik,

T-cell and B-cell Immunology

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 developed SIS-skew to examine development of wild-type and Bcor-deficient siblings of the same clone in parallel. We found Bcor restricted clonal expansion, especially for cDC2s, and suppressed clonal fate potential, especially for pDCs. Therefore, SIS-seq and SIS-skew can reveal the molecular and cellular mechanisms governing clonal fate.