Clonal multi-omics reveals Bcor as a negative regulator of emergency dendritic cell development
Publication Year 2021-04-13,Volume 54,Issue #6,Page 1338-1351.e9
Journal Title
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.
Cell Press
CRISPR minipool; Flt3 ligand; cellular barcoding; clonal lineage tracing; dendritic cell; immunotherapy; single-cell RNA-seq; single-cell fate; state-fate
WEHI Research Division(s)
Immunology; Advanced Technology And Biology; Blood Cells And Blood Cancer; Epigenetics And Development; Population Health And Immunity
PubMed ID
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Creation Date: 2021-05-11 01:58:11
Last Modified: 2021-07-07 11:07:35
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