The chromatin remodeling subunit Baf200 promotes normal hematopoiesis and inhibits leukemogenesis
Journal of Hematology and Oncology, ISSN: 1756-8722, Vol: 11, Issue: 1, Page: 27
2018
- 27Citations
- 40Captures
- 1Mentions
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Metrics Details
- Citations27
- Citation Indexes27
- 27
- CrossRef7
- Captures40
- Readers40
- 39
- Mentions1
- News Mentions1
- 1
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上海巴斯德所发现调控造血发育与白血病发生新机制
Baf200基因的缺失加速了小鼠白血病的发展。(a)建立 MLL-AF9 诱导的急性髓系白血病 (AML) 模型的模式图。(b) 二次建模后野生型小鼠和 Baf200 基因敲除小鼠的生存曲线。 2 月 26 日，中国科学院上海巴斯德研究所张岩研究组、中科院生物化学与细胞生物学研究所周斌研究组、苏州大学熊思东研究组的合作研究成果，以 The chromatin remodeling subunit Baf200 promotes normal hematopoiesis and inhibits leukemogenesis 为题，发表在 Journal of Hematology & Oncology 上。该成果揭示了染色质重塑复合物亚基 Baf200 在调控正常造血和白血病发生中的重要功能。 造血系统发育是一个高度有序而且等级严格的过程，受到转录因子与表观遗传因子的精准调控。ATP 依赖
Article Description
Background: Adenosine triphosphate (ATP)-dependent chromatin remodeling SWI/SNF-like BAF and PBAF complexes have been implicated in the regulation of stem cell function and cancers. Several subunits of BAF or PBAF, including BRG1, BAF53a, BAF45a, BAF180, and BAF250a, are known to be involved in hematopoiesis. Baf200, a subunit of PBAF complex, plays a pivotal role in heart morphogenesis and coronary artery angiogenesis. However, little is known on the importance of Baf200 in normal and malignant hematopoiesis. Methods: Utilizing Tie2-Cre-, Vav-iCre-, and Mx1-Cre-mediated Baf200 gene deletion combined with fetal liver/bone marrow transplantation, we investigated the function of Baf200 in fetal and adult hematopoiesis. In addition, a mouse model of MLL-AF9-driven leukemogenesis was used to study the role of Baf200 in malignant hematopoiesis. We also explored the potential mechanism by using RNA-seq, RT-qPCR, cell cycle, and apoptosis assays. Results: Tie2-Cre-mediated loss of Baf200 causes perinatal death due to defective erythropoiesis and impaired hematopoietic stem cell expansion in the fetal liver. Vav-iCre-mediated loss of Baf200 causes only mild anemia and enhanced extramedullary hematopoiesis. Fetal liver hematopoietic stem cells from Tie2-Cre , Baf200 or Vav-iCre , Baf200 embryos and bone marrow hematopoietic stem cells from Vav-iCre , Baf200 mice exhibited impaired long-term reconstitution potential in vivo. A cell-autonomous requirement of Baf200 for hematopoietic stem cell function was confirmed utilizing the interferon-inducible Mx1-Cre mouse strain. Transcriptomes analysis revealed that expression of several erythropoiesis- and hematopoiesis-associated genes were regulated by Baf200. In addition, loss of Baf200 in a mouse model of MLL-AF9-driven leukemogenesis accelerates the tumor burden and shortens the host survival. Conclusion: Our current studies uncover critical roles of Baf200 in both normal and malignant hematopoiesis and provide a potential therapeutic target for suppressing the progression of leukemia without interfering with normal hematopoiesis.
Bibliographic Details
Springer Science and Business Media LLC
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