BRD9通过调节染色体状态来决定造血干细胞的细胞命运
Muran Xiao1,2, Shinji Kondo3,4, Masaki Nomura1,5
1Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Hyogo, Japan.
Nature communications
|December 15, 2023
概括
非正规的BAF (ncBAF) 综合体,通过其BRD9成分,对于造血干细胞 (HSC) 的命运至关重要. 失去BRD9会改变染色体的可访问性,影响正常和恶性血液形成中的髓状细胞和B细胞发育.
科学领域:
- 细胞和分子生物学 细胞和分子生物学
- 表观遗传学和基因调控
- 血液形成和干细胞生物学
背景情况:
- 依赖ATP的染色体重塑SWI/SNF复合体包括正规BAF (cBAF),多博BAF (PBAF) 和非正规BAF (ncBAF) 的子复合体.
- 虽然在各种细胞类型中已知cBAF和PBAF的功能,但ncBAF在造血干细胞 (HSC) 中的作用仍然未被探索.
- 一个重要的ncBAF成分BRD9在癌症中表现出干扰的表达,包括造血性疾病.
研究的目的:
- 研究BRD9在正常和恶性HSC中的作用.
- 阐明ncBAF通过哪些机制影响HSC中的细胞命运规范.
主要方法:
- 评估了BRD9损失对HSC染色体可访问性和基因表达的影响.
- 研究了BRD9与CTCF的局部化及其对染色质结构的影响.
- 分析了BRD9改变对髓状细胞和B细胞发育的影响.
主要成果:
- BRD9 损失提高了染色质的可访问性,导致骨髓状细胞谱系倾斜和B 细胞发育受损.
- BRD9 损失增加了 CTCF 染色质的招募,改变了拓学关联域内的染色质状态和髓状基因表达.
- 这些发现凸显了ncBAF在HSC命运规范中的关键作用.
结论:
- ncBAF对于通过3D基因组调节来确定HSC中的细胞命运至关重要.
- ncBAF在正常和恶性血液形成中起着重要作用.
- 在HSC中,BRD9是染色质可访问性和谱系承诺的关键调节者.
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