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BRD9 determines the cell fate of hematopoietic stem cells by regulating chromatin state

Author

Listed:
  • Muran Xiao

    (Foundation for Biomedical Research and Innovation at Kobe
    The University of Tokyo)

  • Shinji Kondo

    (National Institute of Genetics
    National Institute of Genetics)

  • Masaki Nomura

    (Foundation for Biomedical Research and Innovation at Kobe
    CiRA Foundation)

  • Shinichiro Kato

    (Nagoya University Graduate School of Medicine
    Nagoya University
    Nagoya University Graduate School of Medicine)

  • Koutarou Nishimura

    (Foundation for Biomedical Research and Innovation at Kobe)

  • Weijia Zang

    (Foundation for Biomedical Research and Innovation at Kobe
    Kyoto University)

  • Yifan Zhang

    (Foundation for Biomedical Research and Innovation at Kobe
    Kyoto University)

  • Tomohiro Akashi

    (Nagoya University Graduate School of Medicine
    Nagoya University)

  • Aaron Viny

    (Columbia University Irving Medical Center)

  • Tsukasa Shigehiro

    (Tokyo University of Science)

  • Tomokatsu Ikawa

    (Tokyo University of Science)

  • Hiromi Yamazaki

    (Foundation for Biomedical Research and Innovation at Kobe)

  • Miki Fukumoto

    (Foundation for Biomedical Research and Innovation at Kobe)

  • Atsushi Tanaka

    (Foundation for Biomedical Research and Innovation at Kobe
    Kyoto University)

  • Yasutaka Hayashi

    (Foundation for Biomedical Research and Innovation at Kobe)

  • Yui Koike

    (Foundation for Biomedical Research and Innovation at Kobe)

  • Yumi Aoyama

    (Foundation for Biomedical Research and Innovation at Kobe
    Kyoto University)

  • Hiromi Ito

    (Foundation for Biomedical Research and Innovation at Kobe)

  • Hiroyoshi Nishikawa

    (Nagoya University Graduate School of Medicine
    Nagoya University
    Nagoya University Graduate School of Medicine
    National Cancer Center)

  • Toshio Kitamura

    (Foundation for Biomedical Research and Innovation at Kobe
    The University of Tokyo)

  • Akinori Kanai

    (Hiroshima University
    The University of Tokyo)

  • Akihiko Yokoyama

    (National Cancer Center)

  • Tohru Fujiwara

    (Tohoku University Graduate School of Medicine
    Tohoku University Hospital)

  • Susumu Goyama

    (The University of Tokyo)

  • Hideki Noguchi

    (National Institute of Genetics
    National Institute of Genetics)

  • Stanley C. Lee

    (Fred Hutchinson Cancer Center
    University of Washington)

  • Atsushi Toyoda

    (National Institute of Genetics
    National Institute of Genetics)

  • Kunihiko Hinohara

    (Nagoya University Graduate School of Medicine
    Nagoya University
    Nagoya University Graduate School of Medicine)

  • Omar Abdel-Wahab

    (Memorial Sloan Kettering Cancer Center)

  • Daichi Inoue

    (Foundation for Biomedical Research and Innovation at Kobe
    Kyoto University)

Abstract

ATP-dependent chromatin remodeling SWI/SNF complexes exist in three subcomplexes: canonical BAF (cBAF), polybromo BAF (PBAF), and a newly described non-canonical BAF (ncBAF). While cBAF and PBAF regulate fates of multiple cell types, roles for ncBAF in hematopoietic stem cells (HSCs) have not been investigated. Motivated by recent discovery of disrupted expression of BRD9, an essential component of ncBAF, in multiple cancers, including clonal hematopoietic disorders, we evaluate here the role of BRD9 in normal and malignant HSCs. BRD9 loss enhances chromatin accessibility, promoting myeloid lineage skewing while impairing B cell development. BRD9 significantly colocalizes with CTCF, whose chromatin recruitment is augmented by BRD9 loss, leading to altered chromatin state and expression of myeloid-related genes within intact topologically associating domains. These data uncover ncBAF as critical for cell fate specification in HSCs via three-dimensional regulation of gene expression and illuminate roles for ncBAF in normal and malignant hematopoiesis.

Suggested Citation

  • Muran Xiao & Shinji Kondo & Masaki Nomura & Shinichiro Kato & Koutarou Nishimura & Weijia Zang & Yifan Zhang & Tomohiro Akashi & Aaron Viny & Tsukasa Shigehiro & Tomokatsu Ikawa & Hiromi Yamazaki & Mi, 2023. "BRD9 determines the cell fate of hematopoietic stem cells by regulating chromatin state," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-44081-6
    DOI: 10.1038/s41467-023-44081-6
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    References listed on IDEAS

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