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

Tian, L; Tomei, S; Schreuder, J; Weber, TS; Amann-Zalcenstein, D; Lin, DS; Tran, J; Audiger, C; Chu, M; Jarratt, A; Willson, T; Hilton, A; Pang, ES; Patton, T; Kelly, M; Su, S; Gouil, Q; Diakumis, P; Bahlo, M; Sargeant, T; Kats, LM; Hodgkin, PD; O&#39;Keeffe, M; Ng, AP; Ritchie, ME; Naik, SH

Author(s): Tian, L; Tomei, S; Schreuder, J; Weber, TS; Amann-Zalcenstein, D; Lin, DS; Tran, J; Audiger, C; Chu, M; Jarratt, A; Willson, T; Hilton, A; Pang, ES; Patton, T; Kelly, M; Su, S; Gouil, Q; Diakumis, P; Bahlo, M; Sargeant, T; Kats, LM; Hodgkin, PD; O'Keeffe, M; Ng, AP; Ritchie, ME; Naik, SH;
Details: Publication Year 2021-04-13,Volume 54,Issue #6,Page 1338-1351.e9
Journal Title: Immunity
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 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.
Publisher: Cell Press
Keywords: CRISPR minipool; Flt3 ligand; cellular barcoding; clonal lineage tracing; dendritic cell; immunotherapy; single-cell RNA-seq; single-cell fate; state-fate
Research Division(s): Immunology; Advanced Technology And Biology; Blood Cells And Blood Cancer; Epigenetics And Development; Population Health And Immunity
PubMed ID: 33862015
Publisher's Version: https://doi.org/10.1016/j.immuni.2021.03.012
NHMRC Grants: NHMRC/1062820, NHMRC/GNT1100033, NHMRC/GNT1101378, NHMRC/GNT1124812, NHMRC/GNT1145184,
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2021-05-11 01:58:11

Last Modified: 2021-07-07 11:07:35