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Blood：KDM4/JMJD2组蛋白去甲基化对造血干细胞的维持至关重要

2019-08-26 MedSci MedSci原创

KDM4JMJD2去甲基化造血干细胞
关注

KDM4/JMJD2是H3K9-和H3K36-特异性去甲基化酶，被认为有望成为携带MLL易位的急性髓系白血病(AML)的治疗靶点。Karl Agger等人研究耗竭KDM4活性对正常造血的长期影响，以探讨持续抑制这些酶的潜在副作用。

中心点：

联合敲除Kdm4a、Kdm4b和Kdm4c可导致造血干细胞缺陷

KDM4去甲基化酶是维持对造血干细胞存活的至关重要的基因持续表达所必需的

摘要：

KDM4/JMJD2是H3K9-和H3K36-特异性去甲基化酶，被认为有望成为携带MLL易位的急性髓系白血病(AML)的治疗靶点。Karl Agger等人研究耗竭KDM4活性对正常造血的长期影响，以探讨持续抑制这些酶的潜在副作用。

利用条件性Kdm4a/Kdm4b/Kdm4c三敲除小鼠，研究人员证实KDM4活性是维持体内造血干细胞(HSC)的必要条件。敲除KDM4去甲基酶导致H3K9me3在转录起始位点积累，并相应下调造血干细胞中多个基因的表达。研究人员发现Taf1b和Nom1两个基友对造血细胞的维持至关重要。

总而言之，本研究表明KDM4去甲基化对维持正常造血至关重要的基因的表达很重要。

原始出处：

Karl Agger，et al. The KDM4/JMJD2 histone demethylases are required for hematopoietic stem cell maintenance.Blood 2019 ：blood.2019000855； doi： https：//doi.org/10.1182/blood.2019000855

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  1. [GetPortalCommentsPageByObjectIdResponse(id=1735752, encodeId=98f41e357525c, content=<a href='/topic/show?id=9c363e259ba' target=_blank style='color:#2F92EE;'>#去甲基化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37259, encryptionId=9c363e259ba, topicName=去甲基化)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=031d33977719, createdName=AspirantSuo, createdTime=Sat Feb 29 00:28:00 CST 2020, time=2020-02-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2028084, encodeId=41112028084b3, content=<a href='/topic/show?id=cc2010448e6' target=_blank style='color:#2F92EE;'>#KDM4#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10448, encryptionId=cc2010448e6, topicName=KDM4)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=49ef408, createdName=hunizi005, createdTime=Fri May 01 03:28:00 CST 2020, time=2020-05-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1025317, encodeId=19ca102531e11, 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=43, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=独孤立克, createdTime=Thu Aug 29 21:28:00 CST 2019, time=2019-08-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1271496, encodeId=392412e1496fa, 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=29, 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=Wed Aug 28 12:28:00 CST 2019, time=2019-08-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1384697, encodeId=9ebc138469e15, content=<a href='/topic/show?id=5c74e7739f0' target=_blank style='color:#2F92EE;'>#组蛋白#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77739, encryptionId=5c74e7739f0, topicName=组蛋白)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ea13490, createdName=xqptu, createdTime=Wed Aug 28 12:28:00 CST 2019, time=2019-08-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1494690, encodeId=cfad149469033, content=<a href='/topic/show?id=084d9499599' target=_blank style='color:#2F92EE;'>#造血#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, 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=Wed Aug 28 12:28:00 CST 2019, time=2019-08-28, status=1, ipAttribution=)]
    2020-02-29 AspirantSuo

    #去甲基化#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1735752, encodeId=98f41e357525c, content=<a href='/topic/show?id=9c363e259ba' target=_blank style='color:#2F92EE;'>#去甲基化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37259, encryptionId=9c363e259ba, topicName=去甲基化)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=031d33977719, createdName=AspirantSuo, createdTime=Sat Feb 29 00:28:00 CST 2020, time=2020-02-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2028084, encodeId=41112028084b3, content=<a href='/topic/show?id=cc2010448e6' target=_blank style='color:#2F92EE;'>#KDM4#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10448, encryptionId=cc2010448e6, topicName=KDM4)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=49ef408, createdName=hunizi005, createdTime=Fri May 01 03:28:00 CST 2020, time=2020-05-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1025317, encodeId=19ca102531e11, 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=43, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=独孤立克, createdTime=Thu Aug 29 21:28:00 CST 2019, time=2019-08-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1271496, encodeId=392412e1496fa, 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=29, 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=Wed Aug 28 12:28:00 CST 2019, time=2019-08-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1384697, encodeId=9ebc138469e15, content=<a href='/topic/show?id=5c74e7739f0' target=_blank style='color:#2F92EE;'>#组蛋白#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77739, encryptionId=5c74e7739f0, topicName=组蛋白)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ea13490, createdName=xqptu, createdTime=Wed Aug 28 12:28:00 CST 2019, time=2019-08-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1494690, encodeId=cfad149469033, content=<a href='/topic/show?id=084d9499599' target=_blank style='color:#2F92EE;'>#造血#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, 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=Wed Aug 28 12:28:00 CST 2019, time=2019-08-28, status=1, ipAttribution=)]
    2020-05-01 hunizi005

    #KDM4#

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1735752, encodeId=98f41e357525c, content=<a href='/topic/show?id=9c363e259ba' target=_blank style='color:#2F92EE;'>#去甲基化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37259, encryptionId=9c363e259ba, topicName=去甲基化)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=031d33977719, createdName=AspirantSuo, createdTime=Sat Feb 29 00:28:00 CST 2020, time=2020-02-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2028084, encodeId=41112028084b3, content=<a href='/topic/show?id=cc2010448e6' target=_blank style='color:#2F92EE;'>#KDM4#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10448, encryptionId=cc2010448e6, topicName=KDM4)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=49ef408, createdName=hunizi005, createdTime=Fri May 01 03:28:00 CST 2020, time=2020-05-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1025317, encodeId=19ca102531e11, 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=43, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=独孤立克, createdTime=Thu Aug 29 21:28:00 CST 2019, time=2019-08-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1271496, encodeId=392412e1496fa, 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=29, 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=Wed Aug 28 12:28:00 CST 2019, time=2019-08-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1384697, encodeId=9ebc138469e15, content=<a href='/topic/show?id=5c74e7739f0' target=_blank style='color:#2F92EE;'>#组蛋白#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77739, encryptionId=5c74e7739f0, topicName=组蛋白)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ea13490, createdName=xqptu, createdTime=Wed Aug 28 12:28:00 CST 2019, time=2019-08-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1494690, encodeId=cfad149469033, content=<a href='/topic/show?id=084d9499599' target=_blank style='color:#2F92EE;'>#造血#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, 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=Wed Aug 28 12:28:00 CST 2019, time=2019-08-28, status=1, ipAttribution=)]
    2019-08-29 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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    2019-08-28 huanbaofeng

    #造血干细胞#

    0

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    2019-08-28 xqptu

    #组蛋白#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1735752, encodeId=98f41e357525c, content=<a href='/topic/show?id=9c363e259ba' target=_blank style='color:#2F92EE;'>#去甲基化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37259, encryptionId=9c363e259ba, topicName=去甲基化)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=031d33977719, createdName=AspirantSuo, createdTime=Sat Feb 29 00:28:00 CST 2020, time=2020-02-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2028084, encodeId=41112028084b3, content=<a href='/topic/show?id=cc2010448e6' target=_blank style='color:#2F92EE;'>#KDM4#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10448, encryptionId=cc2010448e6, topicName=KDM4)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=49ef408, createdName=hunizi005, createdTime=Fri May 01 03:28:00 CST 2020, time=2020-05-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1025317, encodeId=19ca102531e11, 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=43, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=独孤立克, createdTime=Thu Aug 29 21:28:00 CST 2019, time=2019-08-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1271496, encodeId=392412e1496fa, 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=29, 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=Wed Aug 28 12:28:00 CST 2019, time=2019-08-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1384697, encodeId=9ebc138469e15, content=<a href='/topic/show?id=5c74e7739f0' target=_blank style='color:#2F92EE;'>#组蛋白#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77739, encryptionId=5c74e7739f0, topicName=组蛋白)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ea13490, createdName=xqptu, createdTime=Wed Aug 28 12:28:00 CST 2019, time=2019-08-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1494690, encodeId=cfad149469033, content=<a href='/topic/show?id=084d9499599' target=_blank style='color:#2F92EE;'>#造血#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, 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=Wed Aug 28 12:28:00 CST 2019, time=2019-08-28, status=1, ipAttribution=)]
    2019-08-28 俅侠

    #造血#

    0