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Blood:染色质结合蛋白Phf6可限制造血干细胞自我更新

2019-04-14 MedSci MedSci原创

在各种血液病恶性肿瘤中,在X-连锁的PHF6基因上发现重复性的失活突变;PHF6基因编码一种染色质结合转录调节蛋白。但PHF6在正常造血中的作用以及其对肿瘤的抑制作用尚未完全明确。Satoru Miyagi等研究人员建立一种携带漂浮的Phf6等位基因的小鼠,并可在不同发育阶段的造血细胞中失活Phf6。胚胎中Phf6缺失可增强造血干细胞(HSCs)在体外增殖和在受体小鼠中重建造血的能力。新生鼠和成年

在各种血液病恶性肿瘤中,在X-连锁的PHF6基因上发现重复性的失活突变;PHF6基因编码一种染色质结合转录调节蛋白。但PHF6在正常造血中的作用以及其对肿瘤的抑制作用尚未完全明确。

Satoru Miyagi等研究人员建立一种携带漂浮的Phf6等位基因的小鼠,并可在不同发育阶段的造血细胞中失活Phf6。胚胎中Phf6缺失可增强造血干细胞(HSCs)在体外增殖和在受体小鼠中重建造血的能力。

新生鼠和成年鼠缺失Phf6表现为,循环的HSCs容易获得竞争性再种群优势,而休眠的HSCs仅在连续移植后才获得竞争性再种群优势。

Phf6缺陷的HSCs在连续移植过程中可保持较强的再生能力;而且不会诱发任何恶性血液肿瘤。

在机制上,Phf6可直接和间接的激活TNFα信号通路中的下游效应器。敲除Phf6可抑制一些列与TNFα信号相关的基因表达,进而抵抗TNFα介导的对HSCs的生长抑制。

综上所述,本研究表明Phf6可能是HSC自我更新的一种新的负调节因子,提示PHF6的失活性突变可能参与恶性血液肿瘤的发生,但仅有PHF6缺陷并不足以诱导造血细胞转化。

原始出处:

Satoru Miyagi,et al.The chromatin binding protein Phf6 restricts the self-renewal of hematopoietic stem cells.Blood 2019 :blood.2019000468; doi: https://doi.org/10.1182/blood.2019000468 

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    2019-04-16 俅侠
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  6. [GetPortalCommentsPageByObjectIdResponse(id=1805382, encodeId=a080180538254, content=<a href='/topic/show?id=9d42e801133' target=_blank style='color:#2F92EE;'>#细胞自我更新#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78011, encryptionId=9d42e801133, topicName=细胞自我更新)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c859411, createdName=hmwwww, createdTime=Sun May 19 14:42:00 CST 2019, time=2019-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1659320, encodeId=96e8165932068, content=<a href='/topic/show?id=7287861e2ed' target=_blank style='color:#2F92EE;'>#自我更新#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86172, encryptionId=7287861e2ed, topicName=自我更新)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=764624964499, createdName=xsm926, createdTime=Wed Oct 02 21:42:00 CST 2019, time=2019-10-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1271486, encodeId=171e12e148696, content=<a href='/topic/show?id=a0ff950018f' target=_blank style='color:#2F92EE;'>#造血干细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95001, encryptionId=a0ff950018f, topicName=造血干细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e729101, createdName=huanbaofeng, createdTime=Tue Apr 16 13:42:00 CST 2019, time=2019-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1494672, encodeId=5fd414946e2a0, content=<a href='/topic/show?id=084d9499599' target=_blank style='color:#2F92EE;'>#造血#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=94995, encryptionId=084d9499599, topicName=造血)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=caed9138962, createdName=俅侠, createdTime=Tue Apr 16 13:42:00 CST 2019, time=2019-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1575932, encodeId=0bd815e593232, content=<a href='/topic/show?id=dc0e6184243' target=_blank style='color:#2F92EE;'>#染色质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=61842, encryptionId=dc0e6184243, topicName=染色质)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d4ac16256960, createdName=guozhenyu, createdTime=Tue Apr 16 13:42:00 CST 2019, time=2019-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=364674, encodeId=64543646e457, content=谢谢了,学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=112, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=30331616752, createdName=txqjm, createdTime=Mon Apr 15 06:39:05 CST 2019, time=2019-04-15, status=1, ipAttribution=)]
    2019-04-15 txqjm

    谢谢了,学习

    0

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