Blood:内皮蛋白C受体(Epcr)可促进造血干细胞植入Mpl缺陷型小鼠并扩增

2019-02-08 MedSci MedSci原创

中心点:用慢病毒表达Epcr可恢复Mpl缺陷的再生障碍性贫血模型的LT-HSC表型。谱系标志物阴性、Epcr阳性的BM细胞构成了有移植潜力的群体。摘要:Thpo/Mpl信号调控造血干细胞(HSC)的自我更新和静止,但这两个看似对立的功能是如何被调控的,尚无很好的解释。Saskia Kohlscheen等人通过对Mpl缺陷的小鼠模型移植慢病毒转染的造血细胞,来研究已知或预测的Thpo靶基因是否可恢复

中心点:

用慢病毒表达Epcr可恢复Mpl缺陷的再生障碍性贫血模型的LT-HSC表型。

谱系标志物阴性、Epcr阳性的BM细胞构成了有移植潜力的群体。

摘要:

Thpo/Mpl信号调控造血干细胞(HSC)的自我更新和静止,但这两个看似对立的功能是如何被调控的,尚无很好的解释。

Saskia Kohlscheen等人通过对Mpl缺陷的小鼠模型移植慢病毒转染的造血细胞,来研究已知或预测的Thpo靶基因是否可恢复小鼠的Mpl缺失表型。研究人员在检测的基因中发现在Mpl-/-小鼠中,内皮蛋白C受体(Epcr)可扩增HSC,使Mpl-缺陷的骨髓(BM)可进行二次移植。

与对照的Mpc-/-细胞相比,转染Epcr的Mpl-/- HSC在移植后会早早的进入静止期,而且抗凋亡基因Bcl-xL的表达水平上调。同样在野生型的背景下,Epcr表达还可标记骨髓中的移植群体。此外,在Mpc-/-造血过程中,表达Epcr可增加骨髓中巨核细胞的数量。在体外,Thpo可促进Epcr在原代小鼠造血干细胞/祖细胞的表面表达。

综上所述,本研究增加了我们对Thpo信号对HSC移植影响的认知。或有助于对HSC体外操作的管理,或许还可用于基因疗法。


原始出处:

Saskia Kohlscheen, et al. Endothelial protein C receptor supports hematopoietic stem cell engraftment and expansion in Mpl-deficient mice. Blood 2019 :blood-2018-03-837344; doi: https://doi.org/10.1182/blood-2018-03-837344
 
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    2019-09-25 xuyong536
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    2019-02-10 Tommy1950
  5. [GetPortalCommentsPageByObjectIdResponse(id=1773265, encodeId=143a1e7326524, content=<a href='/topic/show?id=5298121e46e' target=_blank style='color:#2F92EE;'>#MPL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12174, encryptionId=5298121e46e, topicName=MPL)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=10e638510530, createdName=xuyong536, createdTime=Wed Sep 25 22:08:00 CST 2019, time=2019-09-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2055186, encodeId=a6492055186e5, content=<a href='/topic/show?id=091688615da' target=_blank style='color:#2F92EE;'>#蛋白C#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88615, encryptionId=091688615da, topicName=蛋白C)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4f2c2500194, createdName=446798725_87912765, createdTime=Sat Mar 16 21:08:00 CST 2019, time=2019-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1271480, encodeId=36cd12e1480fa, 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=40, 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=Sun Feb 10 06:08:00 CST 2019, time=2019-02-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1419425, encodeId=5388141942529, content=<a href='/topic/show?id=e290138682e' target=_blank style='color:#2F92EE;'>#PCR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13868, encryptionId=e290138682e, topicName=PCR)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9cc43496966, createdName=Tommy1950, createdTime=Sun Feb 10 06:08:00 CST 2019, time=2019-02-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1494662, encodeId=ff69149466225, content=<a href='/topic/show?id=084d9499599' target=_blank style='color:#2F92EE;'>#造血#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, 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=Sun Feb 10 06:08:00 CST 2019, time=2019-02-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1520555, encodeId=30aa152055580, content=<a href='/topic/show?id=7a736264553' target=_blank style='color:#2F92EE;'>#植入#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=62645, encryptionId=7a736264553, topicName=植入)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=832411313664, createdName=jiyangfei, createdTime=Sun Feb 10 06:08:00 CST 2019, time=2019-02-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1537082, encodeId=0b12153e0825b, content=<a href='/topic/show?id=9faa6856e9' target=_blank style='color:#2F92EE;'>#Epcr#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6856, encryptionId=9faa6856e9, topicName=Epcr)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cf0c12789666, createdName=ssnine, createdTime=Sun Feb 10 06:08:00 CST 2019, time=2019-02-10, status=1, ipAttribution=)]
    2019-02-10 俅侠
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    2019-02-10 jiyangfei
  7. [GetPortalCommentsPageByObjectIdResponse(id=1773265, encodeId=143a1e7326524, content=<a href='/topic/show?id=5298121e46e' target=_blank style='color:#2F92EE;'>#MPL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12174, encryptionId=5298121e46e, topicName=MPL)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=10e638510530, createdName=xuyong536, createdTime=Wed Sep 25 22:08:00 CST 2019, time=2019-09-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2055186, encodeId=a6492055186e5, content=<a href='/topic/show?id=091688615da' target=_blank style='color:#2F92EE;'>#蛋白C#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88615, encryptionId=091688615da, topicName=蛋白C)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4f2c2500194, createdName=446798725_87912765, createdTime=Sat Mar 16 21:08:00 CST 2019, time=2019-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1271480, encodeId=36cd12e1480fa, 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=40, 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=Sun Feb 10 06:08:00 CST 2019, time=2019-02-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1419425, encodeId=5388141942529, content=<a href='/topic/show?id=e290138682e' target=_blank style='color:#2F92EE;'>#PCR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13868, encryptionId=e290138682e, topicName=PCR)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9cc43496966, createdName=Tommy1950, createdTime=Sun Feb 10 06:08:00 CST 2019, time=2019-02-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1494662, encodeId=ff69149466225, content=<a href='/topic/show?id=084d9499599' target=_blank style='color:#2F92EE;'>#造血#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, 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=Sun Feb 10 06:08:00 CST 2019, time=2019-02-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1520555, encodeId=30aa152055580, content=<a href='/topic/show?id=7a736264553' target=_blank style='color:#2F92EE;'>#植入#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=62645, encryptionId=7a736264553, topicName=植入)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=832411313664, createdName=jiyangfei, createdTime=Sun Feb 10 06:08:00 CST 2019, time=2019-02-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1537082, encodeId=0b12153e0825b, content=<a href='/topic/show?id=9faa6856e9' target=_blank style='color:#2F92EE;'>#Epcr#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6856, encryptionId=9faa6856e9, topicName=Epcr)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cf0c12789666, createdName=ssnine, createdTime=Sun Feb 10 06:08:00 CST 2019, time=2019-02-10, status=1, ipAttribution=)]
    2019-02-10 ssnine

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