SIS-seq data and analysis

Holds the processed data and analysis scripts for paper "Clonal multi-omics approaches reveal Bcor as a negative regulator of emergency dendritic cell development" Despite advances in single cell multi-omics, a single stem or progenitor cell can only be tested once. We have developed ‘clonal multi-omics’, where daughters of a clone act as surrogates of the founder, thereby allowing multiple independent assays per clone. With SIS-seq, clonal siblings are examined in parallel ‘SISter’ assays for gene expression by RNA-seq, or for fate after culture. We identified, then validated using CRISPR, genes that controlled clonal fate bias for different dendritic cell (DC) subtypes. This included Bcor that we identified as a suppressor of plasmacytoid DC (pDC) and conventional DC subtype 2 (cDC2) numbers during Flt3 ligand-mediated ‘emergency’ DC development. With SIS-skew, where WT and BcorKO siblings of the same clone were examined in parallel, we found Bcor restricted clonal expansion, especially to generate 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, including after perturbation.