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An Erg-driven transcriptional program controls B cell lymphopoiesis

Author

Listed:
  • Ashley P. Ng

    (The Walter and Eliza Hall Institute of Medical Research
    The University of Melbourne)

  • Hannah D. Coughlan

    (The University of Melbourne
    The Walter and Eliza Hall Institute of Medical Research)

  • Soroor Hediyeh-zadeh

    (The Walter and Eliza Hall Institute of Medical Research)

  • Kira Behrens

    (The Walter and Eliza Hall Institute of Medical Research)

  • Timothy M. Johanson

    (The University of Melbourne
    The Walter and Eliza Hall Institute of Medical Research)

  • Michael Sze Yuan Low

    (The University of Melbourne
    The Walter and Eliza Hall Institute of Medical Research
    Monash Hospital)

  • Charles C. Bell

    (Peter MacCallum Cancer Centre
    The University of Melbourne)

  • Omer Gilan

    (Peter MacCallum Cancer Centre
    The University of Melbourne)

  • Yih-Chih Chan

    (Peter MacCallum Cancer Centre
    The University of Melbourne)

  • Andrew J. Kueh

    (The Walter and Eliza Hall Institute of Medical Research
    The University of Melbourne)

  • Thomas Boudier

    (The University of Melbourne
    The Walter and Eliza Hall Institute of Medical Research)

  • Rebecca Feltham

    (The Walter and Eliza Hall Institute of Medical Research)

  • Anna Gabrielyan

    (The Walter and Eliza Hall Institute of Medical Research)

  • Ladina DiRago

    (The Walter and Eliza Hall Institute of Medical Research)

  • Craig D. Hyland

    (The Walter and Eliza Hall Institute of Medical Research)

  • Helen Ierino

    (The Walter and Eliza Hall Institute of Medical Research)

  • Sandra Mifsud

    (The Walter and Eliza Hall Institute of Medical Research)

  • Elizabeth Viney

    (The Walter and Eliza Hall Institute of Medical Research)

  • Tracy Willson

    (The Walter and Eliza Hall Institute of Medical Research)

  • Mark A. Dawson

    (Peter MacCallum Cancer Centre
    The University of Melbourne
    The University of Melbourne)

  • Rhys S. Allan

    (The University of Melbourne
    The Walter and Eliza Hall Institute of Medical Research)

  • Marco J. Herold

    (The Walter and Eliza Hall Institute of Medical Research
    The University of Melbourne)

  • Kelly Rogers

    (The University of Melbourne
    The Walter and Eliza Hall Institute of Medical Research)

  • David M. Tarlinton

    (Monash University)

  • Gordon K. Smyth

    (The University of Melbourne
    The Walter and Eliza Hall Institute of Medical Research)

  • Melissa J. Davis

    (The University of Melbourne
    The Walter and Eliza Hall Institute of Medical Research)

  • Stephen L. Nutt

    (The University of Melbourne
    The Walter and Eliza Hall Institute of Medical Research)

  • Warren S. Alexander

    (The Walter and Eliza Hall Institute of Medical Research
    The University of Melbourne)

Abstract

B lymphoid development is initiated by the differentiation of hematopoietic stem cells into lineage committed progenitors, ultimately generating mature B cells. This highly regulated process generates clonal immunological diversity via recombination of immunoglobulin V, D and J gene segments. While several transcription factors that control B cell development and V(D)J recombination have been defined, how these processes are initiated and coordinated into a precise regulatory network remains poorly understood. Here, we show that the transcription factor ETS Related Gene (Erg) is essential for early B lymphoid differentiation. Erg initiates a transcriptional network involving the B cell lineage defining genes, Ebf1 and Pax5, which directly promotes expression of key genes involved in V(D)J recombination and formation of the B cell receptor. Complementation of Erg deficiency with a productively rearranged immunoglobulin gene rescued B lineage development, demonstrating that Erg is an essential and stage-specific regulator of the gene regulatory network controlling B lymphopoiesis.

Suggested Citation

  • Ashley P. Ng & Hannah D. Coughlan & Soroor Hediyeh-zadeh & Kira Behrens & Timothy M. Johanson & Michael Sze Yuan Low & Charles C. Bell & Omer Gilan & Yih-Chih Chan & Andrew J. Kueh & Thomas Boudier & , 2020. "An Erg-driven transcriptional program controls B cell lymphopoiesis," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16828-y
    DOI: 10.1038/s41467-020-16828-y
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    Cited by:

    1. Yexuan Deng & Sarah T. Diepstraten & Margaret A. Potts & Göknur Giner & Stephanie Trezise & Ashley P. Ng & Gerry Healey & Serena R. Kane & Amali Cooray & Kira Behrens & Amy Heidersbach & Andrew J. Kue, 2022. "Generation of a CRISPR activation mouse that enables modelling of aggressive lymphoma and interrogation of venetoclax resistance," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Chen Chen & Bongsoo Park & Emeline Ragonnaud & Monica Bodogai & Xin Wang & Le Zong & Jung-Min Lee & Isabel Beerman & Arya Biragyn, 2022. "Cancer co-opts differentiation of B-cell precursors into macrophage-like cells," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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