Blood：SRC-3通过调节线粒体代谢参与维持造血干细胞的静止状态

2018-07-02 MedSci MedSci原创

静止维持是造血干细胞（HSCs）的重要特性，但HSC静止维持所涉及的调控因子和潜在机制尚未完全明确。Mengjia Hu等人发现类固醇受体共激活剂3（SRC-3）在HSCs中高表达，而SRC-3缺陷的HSCs表现为静止减少、增殖活跃，导致对化疗和放疗的敏感性增加。此外，在缺乏SRC-3的情况下，HSCs的长期重构能力显着受损，SRC-3敲除（SRC-/-）小鼠表现为造血干细胞和祖细胞稳态显著被破坏

静止维持是造血干细胞（HSCs）的重要特性，但HSC静止维持所涉及的调控因子和潜在机制尚未完全明确。Mengjia Hu等人发现类固醇受体共激活剂3（SRC-3）在HSCs中高表达，而SRC-3缺陷的HSCs表现为静止减少、增殖活跃，导致对化疗和放疗的敏感性增加。此外，在缺乏SRC-3的情况下，HSCs的长期重构能力显着受损，SRC-3敲除（SRC-/-）小鼠表现为造血干细胞和祖细胞稳态显著被破坏。

进一步研究发现SRC缺陷可导致HSCs线粒体代谢增强，伴随活性氧产生过量。值得注意地是，在SRC-3缺陷型HSCs中，参与线粒体代谢调控的过氧化物酶体增生物激活的受体共激活剂1α（PGC-1α）的下游靶基因的表达显著上调。与此同时，在SRC-3无效的HSCs中观察到组蛋白乙酰转移酶GCN5的表达明显降低，伴随PGC-1α乙酰化作用减弱。相反，过表达GCN5可抑制SRC-3缺陷所诱导的线粒体代谢增强和ROS过量产生，进而明显恢复SRC-3-/-小鼠受损的HSCs。

总而言之，本研究表明SRC-3通过调节线粒体代谢在HSC静止维持中发挥重要作用。

原始出处：

Mengjia Hu，et al. SRC-3 is involved in maintaining hematopoietic stem cell quiescence by regulation of mitochondrial metabolism in mice. Blood 2018 ：blood-2018-02-831669； doi： https：//doi.org/10.1182/blood-2018-02-831669

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2019-02-16 zhangxingru

#SRC#

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2018-10-27 yuandd

#静止状态#

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2018-10-05 shalley66

#线粒体代谢#

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2018-07-04 huanbaofeng

#造血干细胞#

25 0
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2018-07-04 俅侠

#造血#

31 0
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2018-07-02 惠映实验室

学习了.谢谢分享.

49 0
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2018-07-02 虈亣靌

看看

32 0

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