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Clonal multi-omics reveals Bcor as a negative regulator of emergency dendritic cell development.
Tian, Luyi; Tomei, Sara; Schreuder, Jaring; Weber, Tom S; Amann-Zalcenstein, Daniela; Lin, Dawn S; Tran, Jessica; Audiger, Cindy; Chu, Mathew; Jarratt, Andrew; Willson, Tracy; Hilton, Adrienne; Pang, Ee Shan; Patton, Timothy; Kelly, Madison; Su, Shian; Gouil, Quentin; Diakumis, Peter; Bahlo, Melanie; Sargeant, Toby; Kats, Lev M; Hodgkin, Philip D; O'Keeffe, Meredith; Ng, Ashley P; Ritchie, Matthew E; Naik, Shalin H.
Affiliation
  • Tian L; Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Epigenetics and Development Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkvil
  • Tomei S; Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia.
  • Schreuder J; Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Weber TS; Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia.
  • Amann-Zalcenstein D; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia; Single Cell Open Research Endeavour (SCORE), The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Lin DS; Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia.
  • Tran J; Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Audiger C; Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia.
  • Chu M; Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Jarratt A; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia; Blood Cells and Blood Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Willson T; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia; Blood Cells and Blood Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Hilton A; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia; Blood Cells and Blood Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Pang ES; Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
  • Patton T; Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
  • Kelly M; The Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3052, Australia.
  • Su S; Epigenetics and Development Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia.
  • Gouil Q; Epigenetics and Development Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia.
  • Diakumis P; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia; Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Bahlo M; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia; Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Sargeant T; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia; Blood Cells and Blood Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Kats LM; The Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3052, Australia.
  • Hodgkin PD; Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia.
  • O'Keeffe M; Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
  • Ng AP; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia; Blood Cells and Blood Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Ritchie ME; Epigenetics and Development Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia.
  • Naik SH; Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia; Single Cell Open Research Endeavour (SCORE), The Walter and Eliza Hall Institute of Medical Research,
Immunity ; 54(6): 1338-1351.e9, 2021 06 08.
Article in En | MEDLINE | ID: mdl-33862015
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Repressor Proteins / Dendritic Cells / Proto-Oncogene Proteins Type of study: Prognostic_studies Limits: Animals / Female / Humans / Male Language: En Journal: Immunity Journal subject: ALERGIA E IMUNOLOGIA Year: 2021 Document type: Article Country of publication:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Repressor Proteins / Dendritic Cells / Proto-Oncogene Proteins Type of study: Prognostic_studies Limits: Animals / Female / Humans / Male Language: En Journal: Immunity Journal subject: ALERGIA E IMUNOLOGIA Year: 2021 Document type: Article Country of publication: