In-depth functional analysis of BRD9 in fetal hematopoiesis reveals context-dependent roles
The hierarchical organization of hematopoietic stem cells (HSCs) governing adult hematopoiesis has been extensively investigated. However, the dynamic epigenomic transition from fetal to adult hematopoiesis remains incompletely understood, particularly regarding the involvement of epigenetic factors. In this study, we investigate the roles of BRD9, an essential component of the non-canonical BAF (ncBAF) complex known to govern the fate of adult HSCs, in fetal hematopoiesis. Consistent with observations in adult hematopoiesis, BRD9 loss impairs fetal HSC stemness and disturbs erythroid maturation. Intriguingly, the impact on myeloid lineage was discrepant: BRD9 loss inhibited and promoted myeloid differentiation in fetal and adult models, respectively. Through comprehensive transcriptomic and epigenomic analysis, we elucidate the differential roles of BRD9 in a context- and lineage-dependent manner. Our data uncover how BRD9/ncBAF complex modulates transcription in a stage-specific manner, providing deeper insights into the epigenetic regulation underlying the transition from fetal to adult hematopoiesis.
Authors
- Chihiro Hasegawa
- Muran Xiao
- Koutarou Nishimura
- Akifumi Takaori‐Kondo (ORCID: https://orcid.org/0000-0001-7678-4284)
- Yumi Aoyama
- Wataru Saika (ORCID: https://orcid.org/0000-0001-7960-9246)
- Weijia Zang
- Daichi Inoue (ORCID: https://orcid.org/0000-0002-7947-6540)
- Masaki Nomura (ORCID: https://orcid.org/0000-0003-1277-9122)
- Miki Fukumoto
- Yifan Zhang (ORCID: https://orcid.org/0000-0002-0283-0468)
- Atsushi Tanaka (ORCID: https://orcid.org/0000-0002-9449-4894)
- Hiromi Ito (ORCID: https://orcid.org/0000-0002-9022-7780)
- Yui Koike (ORCID: https://orcid.org/0000-0002-4470-6350)
- Hiromi Yamazaki (ORCID: https://orcid.org/0000-0002-3845-2657)
Institutions
- Shiga University of Medical Science (JP)
- Kyoto University (JP)
- Ube Frontier University (JP)
- Foundation for Biomedical Research and Innovation (JP)
- The University of Osaka (JP)
Publication Details
- Journal
- iScience
- Published
- 2025-02-12
- DOI
- https://doi.org/10.1016/j.isci.2025.112010
- Citations
- 4
- Primary Topic
- Chromatin Remodeling and Cancer
- Type
- article
- Field-Weighted Citation Impact
- 3.22
Funders
- Naito Foundation
- Takeda Science Foundation
- Cell Science Research Foundation
- Sumitomo Foundation
- Uehara Memorial Foundation
- Japan Agency for Medical Research and Development
- Friends of Leukemia Research Fund
- Japanese Society of Hematology
- Mitsubishi Foundation
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Kobayashi Foundation for Cancer Research
- Princess Takamatsu Cancer Research Fund
- Foundation for Biomedical Research and Innovation
- Ono Pharmaceutical
- MSD Life Science Foundation, Public Interest Incorporated Foundation
- Japan Society for the Promotion of Science
- Japan Science and Technology Agency
- Core Research for Evolutional Science and Technology
- Exploratory Research for Advanced Technology