Nature Communications (Dec 2023)
BRD9 determines the cell fate of hematopoietic stem cells by regulating chromatin state
- Muran Xiao,
- Shinji Kondo,
- Masaki Nomura,
- Shinichiro Kato,
- Koutarou Nishimura,
- Weijia Zang,
- Yifan Zhang,
- Tomohiro Akashi,
- Aaron Viny,
- Tsukasa Shigehiro,
- Tomokatsu Ikawa,
- Hiromi Yamazaki,
- Miki Fukumoto,
- Atsushi Tanaka,
- Yasutaka Hayashi,
- Yui Koike,
- Yumi Aoyama,
- Hiromi Ito,
- Hiroyoshi Nishikawa,
- Toshio Kitamura,
- Akinori Kanai,
- Akihiko Yokoyama,
- Tohru Fujiwara,
- Susumu Goyama,
- Hideki Noguchi,
- Stanley C. Lee,
- Atsushi Toyoda,
- Kunihiko Hinohara,
- Omar Abdel-Wahab,
- Daichi Inoue
Affiliations
- Muran Xiao
- Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe
- Shinji Kondo
- Center for Genome Informatics, Joint Support-Center for Data Science Research, Research Organization of Information and Systems, National Institute of Genetics
- Masaki Nomura
- Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe
- Shinichiro Kato
- Department of Immunology, Nagoya University Graduate School of Medicine
- Koutarou Nishimura
- Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe
- Weijia Zang
- Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe
- Yifan Zhang
- Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe
- Tomohiro Akashi
- Center for 5D Cell Dynamics, Nagoya University Graduate School of Medicine
- Aaron Viny
- Department of Medicine, Division of Hematology and Oncology, and Department of Genetics and Development, Columbia University Irving Medical Center
- Tsukasa Shigehiro
- Division of Immunobiology, Research Institute for Biomedical Sciences, Tokyo University of Science
- Tomokatsu Ikawa
- Division of Immunobiology, Research Institute for Biomedical Sciences, Tokyo University of Science
- Hiromi Yamazaki
- Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe
- Miki Fukumoto
- Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe
- Atsushi Tanaka
- Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe
- Yasutaka Hayashi
- Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe
- Yui Koike
- Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe
- Yumi Aoyama
- Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe
- Hiromi Ito
- Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe
- Hiroyoshi Nishikawa
- Department of Immunology, Nagoya University Graduate School of Medicine
- Toshio Kitamura
- Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe
- Akinori Kanai
- Department of Molecular Oncology and Leukemia Program Project, Research Institute for Radiation Biology and Medicine, Hiroshima University
- Akihiko Yokoyama
- Tsuruoka Metabolomics Laboratory, National Cancer Center
- Tohru Fujiwara
- Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine
- Susumu Goyama
- Division of Molecular Oncology, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo
- Hideki Noguchi
- Center for Genome Informatics, Joint Support-Center for Data Science Research, Research Organization of Information and Systems, National Institute of Genetics
- Stanley C. Lee
- Clinical Research Division, Fred Hutchinson Cancer Center
- Atsushi Toyoda
- Advanced Genomics Center, National Institute of Genetics
- Kunihiko Hinohara
- Department of Immunology, Nagoya University Graduate School of Medicine
- Omar Abdel-Wahab
- Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center
- Daichi Inoue
- Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe
- DOI
- https://doi.org/10.1038/s41467-023-44081-6
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 22
Abstract
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.
