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Blood:Yap1-Scribble极化决定了造血干细胞的命运

2020-06-07 QQT MedSci原创

造血干细胞对应激的适应反应取决于Yap1/Taz;在HSC命运决定中,Scribble连接Cdc42和Hippo信号级联的胞质功能。

YAP1及其类似物Taz在很大程度上可控制上皮组织的生长。Althoff等已经确认造血干细胞(HSC)对应激的适应性反应取决于YAP1和Taz。

YAP1和Taz缺失可导致HSC静止丧失、对称的自我更新能力,使HSC更容易受到系列清髓性5-氟尿嘧啶治疗的影响。这一效应依赖于YAP1通过其PDZ结构域介导的与脚手架Scribble的相互作用而主导的胞浆极化。

Scrible和YAP1协同控制胞质Cdc42的活性和体内HSC的命运决定。Scribble缺失可破坏YAP1与Cdc42的共极化,减弱Cdc42的活性,从而导致具有竞争重建优势的自我更新中的HSC增多。

上述数据表明,Scribble/YAP1共极化对CdC42依赖的HSC不对称分裂和命运活性是必不可少的。Scribble、YAP1和Taz联合缺失可导致Rac特异性鸟嘌呤核苷酸交换因子的转录上调、Rac激活和HSC适应性恢复。Scrible将Cdc42与Hippo信号级联的胞浆功能联系在一起,决定了HSC的命运。

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  1. [GetPortalCommentsPageByObjectIdResponse(id=1793694, encodeId=f04e1e93694e0, content=<a href='/topic/show?id=d1741606614' target=_blank style='color:#2F92EE;'>#Scrib#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16066, encryptionId=d1741606614, topicName=Scrib)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=baf586, createdName=wangbingxhy, createdTime=Fri Feb 19 19:31:35 CST 2021, time=2021-02-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2081922, encodeId=622d2081922dc, content=<a href='/topic/show?id=c2971893397' target=_blank style='color:#2F92EE;'>#YAP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18933, encryptionId=c2971893397, topicName=YAP)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3333505, createdName=gujh, createdTime=Wed Aug 19 23:31:35 CST 2020, time=2020-08-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1715758, encodeId=20631e1575889, content=<a href='/topic/show?id=24051893e0f' target=_blank style='color:#2F92EE;'>#YAP1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18937, encryptionId=24051893e0f, topicName=YAP1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=941632034462, createdName=xinmeili, createdTime=Mon Dec 14 15:31:35 CST 2020, time=2020-12-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1025465, encodeId=570c102546586, content=干细胞是热点,但是进入临床仍然需要时间和临床疗效验证哦, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=独孤立克, createdTime=Wed Jun 10 21:31:35 CST 2020, time=2020-06-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1271518, encodeId=1f9412e15183f, 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=72, 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 Jun 09 12:31:35 CST 2020, time=2020-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1494736, encodeId=32411494e363c, content=<a href='/topic/show?id=084d9499599' target=_blank style='color:#2F92EE;'>#造血#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, 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 Jun 09 12:31:35 CST 2020, time=2020-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1614867, encodeId=fa1a161486e98, content=<a href='/topic/show?id=af2116063a2' target=_blank style='color:#2F92EE;'>#SCR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16063, encryptionId=af2116063a2, topicName=SCR)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=914b19549580, createdName=12498877m104暂无昵称, createdTime=Tue Jun 09 12:31:35 CST 2020, time=2020-06-09, status=1, ipAttribution=)]
    2021-02-19 wangbingxhy
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    2020-08-19 gujh
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    2020-12-14 xinmeili
  4. [GetPortalCommentsPageByObjectIdResponse(id=1793694, encodeId=f04e1e93694e0, content=<a href='/topic/show?id=d1741606614' target=_blank style='color:#2F92EE;'>#Scrib#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16066, encryptionId=d1741606614, topicName=Scrib)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=baf586, createdName=wangbingxhy, createdTime=Fri Feb 19 19:31:35 CST 2021, time=2021-02-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2081922, encodeId=622d2081922dc, content=<a href='/topic/show?id=c2971893397' target=_blank style='color:#2F92EE;'>#YAP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18933, encryptionId=c2971893397, topicName=YAP)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3333505, createdName=gujh, createdTime=Wed Aug 19 23:31:35 CST 2020, time=2020-08-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1715758, encodeId=20631e1575889, content=<a href='/topic/show?id=24051893e0f' target=_blank style='color:#2F92EE;'>#YAP1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18937, encryptionId=24051893e0f, topicName=YAP1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=941632034462, createdName=xinmeili, createdTime=Mon Dec 14 15:31:35 CST 2020, time=2020-12-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1025465, encodeId=570c102546586, content=干细胞是热点,但是进入临床仍然需要时间和临床疗效验证哦, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=独孤立克, createdTime=Wed Jun 10 21:31:35 CST 2020, time=2020-06-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1271518, encodeId=1f9412e15183f, 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=72, 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 Jun 09 12:31:35 CST 2020, time=2020-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1494736, encodeId=32411494e363c, content=<a href='/topic/show?id=084d9499599' target=_blank style='color:#2F92EE;'>#造血#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, 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 Jun 09 12:31:35 CST 2020, time=2020-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1614867, encodeId=fa1a161486e98, content=<a href='/topic/show?id=af2116063a2' target=_blank style='color:#2F92EE;'>#SCR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16063, encryptionId=af2116063a2, topicName=SCR)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=914b19549580, createdName=12498877m104暂无昵称, createdTime=Tue Jun 09 12:31:35 CST 2020, time=2020-06-09, status=1, ipAttribution=)]
    2020-06-10 独孤立克

    干细胞是热点,但是进入临床仍然需要时间和临床疗效验证哦

    0

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    2020-06-09 俅侠
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