Nature发现:让血液干细胞在体外大量繁殖的关键蛋白

2019-12-03 佚名 中国生物技术网

近日,发表在《Nature》上的一项研究中,美国加州大学洛杉矶分校(UCLA)的科学家团队发现了一种蛋白质与人类血液干细胞自我更新能力之间的联系。激活该蛋白可以血液干细胞在实验室条件下自我更新至少12倍!

近日,发表在《Nature》上的一项研究中,美国加州大学洛杉矶分校(UCLA)的科学家团队发现了一种蛋白质与人类血液干细胞自我更新能力之间的联系。激活该蛋白可以血液干细胞在实验室条件下自我更新至少12倍!

在人体外条件下增殖血液干细胞可以极大地改善血癌(如白血病)和许多遗传性血液疾病的治疗选择。

该研究通讯作者、UCLA的Eli和Edythe再生医学与干细胞研究中心细胞和发育生物学教授Hanna Mikkola博士研究血液干细胞已有二十余年。她说:“尽管多年来我们已经对这些细胞的生物学特性了解很多,但一个关键挑战仍然存在,即让人类血液干细胞在实验室中自我更新。我们必须克服这一障碍才能推动这一领域向前发展。”

血液干细胞(也称为造血干细胞)存在于骨髓中,在那里它们自我更新并分化为各种类型的血细胞。几十年来,骨髓移植一直被用于治疗血液或免疫系统的某些疾病。但是,骨髓移植具有明显的局限性:找到一个相容的骨髓供体并不总是存在的,患者的免疫系统可能排斥异源细胞,并且移植的干细胞数量可能不足以成功治疗疾病。

将血液干细胞从骨髓中取出并放在实验室培养皿中后,它们很快就会失去自我更新的能力,或死亡,或分化为其他类型的血细胞。Mikkola的目标是在实验室受控条件下使血液干细胞自我更新,这将为治疗许多血液疾病开辟更多新的可能性,其中包括对患者自身血液干细胞进行更安全的基因工程改造。它还可以使科学家从多能干细胞生产血液干细胞,而这些干细胞具有在体内产生任何细胞类型的潜力。

为了找到让血液干细胞在实验室中自我更新的方法,研究人员分析了当人类血液干细胞失去自我更新能力时会关闭的基因,并指出当血液干细胞分化为特定血细胞(如白细胞或红细胞)时哪些基因会关闭。然后他们将血液干细胞放入实验室培养皿中观察。他们还利用多能干细胞,制造出缺乏自我更新能力的血液干细胞样细胞,并监测哪些基因未被激活。

他们发现,MLLT3基因的表达与血液干细胞的自我更新能力密切相关,并且MLLT3基因产生的蛋白质为血液干细胞提供了维持其自我更新能力所需的指令。它通过与其他调节蛋白共同作用来保持血液干细胞的重要部分在细胞分裂时正常运作。

进一步,研究人员想确定,在实验室培养皿中维持血液干细胞中MLLT3蛋白的水平是否足以提高其自我更新能力。为此,该团队使用一种病毒载体(一种经过特殊修饰的病毒,可以将遗传信息携带到细胞核而不引起疾病)将一个活跃的MLLT3基因插入血液干细胞中,并观察到功能性血液干细胞在实验室培养皿中可以繁殖至少12倍。

Mikkola说:“治疗一名患者所需的血液干细胞数量极其庞大。但我们不只是关注数量,我们还需要确保实验室制造的血液干细胞在移植时可以通过制造所有类型的血细胞来继续正常工作。”

最近其他研究已经鉴定出一些小分子(通常用于制造药物的有机化合物)有助于人类血液干细胞在实验室中繁殖。当Mikkola的团队使用这些小分子时,他们观察到血液干细胞的自我更新总体上有所改善,但是这些细胞不能维持适当的MLLT3水平,并且在移植到小鼠体内后也不能很好地发挥作用。

UCLA项目科学家、该研究的共同通讯作者Vincenzo Calvanese说:“先前关于小分子的发现非常重要,我们正在以此为基础进行研究。我们的方法将血液干细胞暴露在这些小分子中,并插入一段活跃的MLLT3基因,从而创造出可以很好融入小鼠骨髓的血液干细胞,有效地产生所有类型的血细胞,并保持它们的自我更新能力。”

重要的是,MLLT3使血液干细胞以安全的速率自我更新,它们没有任何危险的特征,如增殖过多或突变并产生可能导致白血病的异常细胞。

研究人员的下一步研究包括确定血液干细胞DNA中的哪些蛋白质和元素会影响MLLT3的开关,以及如何使用实验室培养皿中的成分对其进行控制。有了这些信息,他们就有可能找到无需使用病毒载体即可打开和关闭MLLT3的方法,这种方法在临床环境中更安全。

原始出处:
Vincenzo Calvanese, Andrew T Nguyen , Hanna K A Mikkola ,et al.MLLT3 Governs Human Haematopoietic Stem-Cell Self-Renewal and Engraftment.Nature .2019 Nov 27.PMID: 31776511 DOI: 10.1038/s41586-019-1790-2

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    2020-07-21 liye789132251
  4. [GetPortalCommentsPageByObjectIdResponse(id=2027625, encodeId=c251202e62503, content=<a href='/topic/show?id=fd08301865e' target=_blank style='color:#2F92EE;'>#关键蛋白#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=30186, encryptionId=fd08301865e, topicName=关键蛋白)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d8e0333, createdName=zhangyxzsh, createdTime=Fri Sep 18 16:57:00 CST 2020, time=2020-09-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2080004, encodeId=79d6208000438, content=<a href='/topic/show?id=6a08892e1a7' target=_blank style='color:#2F92EE;'>#血液干细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89271, encryptionId=6a08892e1a7, topicName=血液干细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45b2276, createdName=839640778, createdTime=Fri Jul 31 20:57:00 CST 2020, time=2020-07-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1884024, encodeId=89651884024bb, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Tue Jul 21 23:57:00 CST 2020, time=2020-07-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1025368, encodeId=b46b10253685e, 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=31, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=独孤立克, createdTime=Fri Dec 06 14:57:00 CST 2019, time=2019-12-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=376422, encodeId=5a543e6422ef, content=研究新颖,受益良多, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7b005228115, createdName=14794e5bm67(暂无昵称), createdTime=Tue Dec 03 18:47:50 CST 2019, time=2019-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=376421, encodeId=328e3e642160, content=研究新颖,受益良多, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7b005228115, createdName=14794e5bm67(暂无昵称), createdTime=Tue Dec 03 18:47:48 CST 2019, time=2019-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=376420, encodeId=1eba3e642040, content=研究新颖,受益良多, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7b005228115, createdName=14794e5bm67(暂无昵称), createdTime=Tue Dec 03 18:47:46 CST 2019, time=2019-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=376419, encodeId=674b3e64197d, content=研究新颖,受益良多, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7b005228115, createdName=14794e5bm67(暂无昵称), createdTime=Tue Dec 03 18:47:43 CST 2019, time=2019-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=376418, encodeId=0fc23e6418d5, content=研究新颖,受益良多, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7b005228115, createdName=14794e5bm67(暂无昵称), createdTime=Tue Dec 03 18:47:40 CST 2019, time=2019-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=376417, encodeId=c8903e641709, content=研究新颖,受益良多, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7b005228115, createdName=14794e5bm67(暂无昵称), createdTime=Tue Dec 03 18:47:37 CST 2019, time=2019-12-03, status=1, ipAttribution=)]
    2019-12-06 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

  5. [GetPortalCommentsPageByObjectIdResponse(id=2027625, encodeId=c251202e62503, content=<a href='/topic/show?id=fd08301865e' target=_blank style='color:#2F92EE;'>#关键蛋白#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=30186, encryptionId=fd08301865e, topicName=关键蛋白)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d8e0333, createdName=zhangyxzsh, createdTime=Fri Sep 18 16:57:00 CST 2020, time=2020-09-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2080004, encodeId=79d6208000438, content=<a href='/topic/show?id=6a08892e1a7' target=_blank style='color:#2F92EE;'>#血液干细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89271, encryptionId=6a08892e1a7, topicName=血液干细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45b2276, createdName=839640778, createdTime=Fri Jul 31 20:57:00 CST 2020, time=2020-07-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1884024, encodeId=89651884024bb, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Tue Jul 21 23:57:00 CST 2020, time=2020-07-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1025368, encodeId=b46b10253685e, 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=31, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=独孤立克, createdTime=Fri Dec 06 14:57:00 CST 2019, time=2019-12-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=376422, encodeId=5a543e6422ef, content=研究新颖,受益良多, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7b005228115, createdName=14794e5bm67(暂无昵称), createdTime=Tue Dec 03 18:47:50 CST 2019, time=2019-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=376421, encodeId=328e3e642160, content=研究新颖,受益良多, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7b005228115, createdName=14794e5bm67(暂无昵称), createdTime=Tue Dec 03 18:47:48 CST 2019, time=2019-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=376420, encodeId=1eba3e642040, content=研究新颖,受益良多, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7b005228115, createdName=14794e5bm67(暂无昵称), createdTime=Tue Dec 03 18:47:46 CST 2019, time=2019-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=376419, encodeId=674b3e64197d, content=研究新颖,受益良多, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7b005228115, createdName=14794e5bm67(暂无昵称), createdTime=Tue Dec 03 18:47:43 CST 2019, time=2019-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=376418, encodeId=0fc23e6418d5, content=研究新颖,受益良多, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7b005228115, createdName=14794e5bm67(暂无昵称), createdTime=Tue Dec 03 18:47:40 CST 2019, time=2019-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=376417, encodeId=c8903e641709, content=研究新颖,受益良多, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7b005228115, createdName=14794e5bm67(暂无昵称), createdTime=Tue Dec 03 18:47:37 CST 2019, time=2019-12-03, status=1, ipAttribution=)]
    2019-12-03 14794e5bm67(暂无昵称)

    研究新颖,受益良多

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=2027625, encodeId=c251202e62503, content=<a href='/topic/show?id=fd08301865e' target=_blank style='color:#2F92EE;'>#关键蛋白#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=30186, encryptionId=fd08301865e, topicName=关键蛋白)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d8e0333, createdName=zhangyxzsh, createdTime=Fri Sep 18 16:57:00 CST 2020, time=2020-09-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2080004, encodeId=79d6208000438, content=<a href='/topic/show?id=6a08892e1a7' target=_blank style='color:#2F92EE;'>#血液干细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89271, encryptionId=6a08892e1a7, topicName=血液干细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45b2276, createdName=839640778, createdTime=Fri Jul 31 20:57:00 CST 2020, time=2020-07-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1884024, encodeId=89651884024bb, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Tue Jul 21 23:57:00 CST 2020, time=2020-07-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1025368, encodeId=b46b10253685e, 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=31, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=独孤立克, createdTime=Fri Dec 06 14:57:00 CST 2019, time=2019-12-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=376422, encodeId=5a543e6422ef, content=研究新颖,受益良多, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7b005228115, createdName=14794e5bm67(暂无昵称), createdTime=Tue Dec 03 18:47:50 CST 2019, time=2019-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=376421, encodeId=328e3e642160, content=研究新颖,受益良多, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7b005228115, createdName=14794e5bm67(暂无昵称), createdTime=Tue Dec 03 18:47:48 CST 2019, time=2019-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=376420, encodeId=1eba3e642040, content=研究新颖,受益良多, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7b005228115, createdName=14794e5bm67(暂无昵称), createdTime=Tue Dec 03 18:47:46 CST 2019, time=2019-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=376419, encodeId=674b3e64197d, content=研究新颖,受益良多, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7b005228115, createdName=14794e5bm67(暂无昵称), createdTime=Tue Dec 03 18:47:43 CST 2019, time=2019-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=376418, encodeId=0fc23e6418d5, content=研究新颖,受益良多, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7b005228115, createdName=14794e5bm67(暂无昵称), createdTime=Tue Dec 03 18:47:40 CST 2019, time=2019-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=376417, encodeId=c8903e641709, content=研究新颖,受益良多, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7b005228115, createdName=14794e5bm67(暂无昵称), createdTime=Tue Dec 03 18:47:37 CST 2019, time=2019-12-03, status=1, ipAttribution=)]
    2019-12-03 14794e5bm67(暂无昵称)

    研究新颖,受益良多

    0

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    2019-12-03 14794e5bm67(暂无昵称)

    研究新颖,受益良多

    0

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    2019-12-03 14794e5bm67(暂无昵称)

    研究新颖,受益良多

    0

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    2019-12-03 14794e5bm67(暂无昵称)

    研究新颖,受益良多

    0

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    2019-12-03 14794e5bm67(暂无昵称)

    研究新颖,受益良多

    0

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