Cell Stem Cell:你的减肥药适不适合你?Cell子刊提出一种新评估方法

2018-04-21 小通 生物通

美国Cedars-Sinai医学中心的科学家们通过一项新技术研究肥胖患者的大脑神经元,这将有助于制定更加个性化的肥胖症治疗方法。

美国Cedars-Sinai医学中心的科学家们通过一项新技术研究肥胖患者的大脑神经元,这将有助于制定更加个性化的肥胖症治疗方法。


两种类型的下丘脑神经元(洋红色和青色),这些神经元是通过诱导多能干细胞分化而来

这一研究成果公布在Cell Stem Cell杂志上。

文章作者,Cedars-Sinai医学中心助理教授Dhruv Sareen博士说:“我们已经迈出了构建里程碑平台的第一步,这种平台可以评估实验性治疗对特定患者的影响。最终,这将为个性化医疗铺平道路,可以针对具有不同遗传背景和疾病状态的肥胖患者进行定制减肥药物。”


Dhruv Sareen, PhD

统计数据显示,超过三分之一的美国成年人患有肥胖症,这令他们患心脏病,中风,糖尿病和某些癌症的风险增高。

这项新研究集中在大脑下丘脑区域,这一区域调节饥饿,口渴,体温和其他需要激素控制的功能。此前的一些研究表明肥胖可能部分由某些下丘脑神经元的基因突变引起。这些神经元能对影响代谢和帮助大脑和胃肠道相互沟通的化学物质产生应答。当这些神经元出问题时,我们身体可能无法感觉到自己已经饱了,应该停止进食了,从而导致体重增加。

Sareen说:“了解这种信号传导过程如何在细胞水平上起作用,对于未来肥胖治疗策略提供了重要的线索。但是这个过程很难研究,因为活体患者的下丘脑组织不容易进行直接检查。”

这项新研究利用干细胞技术在体外构建了下丘脑神经元,部分解决了这一问题。

为了进行分析,研究人员从5名超重肥胖者和7名体重正常的个体中采集血液和皮肤细胞。

其中超肥胖定义为体重指数为50或更高(正常评分低于25)。研究人员将这些细胞重编程为诱导多能干细胞(iPSC),也就是可以生成任何类型的细胞。iPSC被诱导产生特殊的下丘脑神经元,这种“培养皿中的神经元”与原始细胞来源的个体患者的遗传学相一致。

当研究者将超级肥胖个体iPSC产生的神经元与正常体重个体的神经元进行比较时,他们发现了显着差异。超级肥胖神经元含有多个基因突变,并且在调节饥饿,饱食和代谢的几种激素反应上出现了异常。

“这些研究结果表明,iPSC技术是研究肥胖,以及基因和环境之间相互作用如何影响其发展的重要方法,”Sareen说,“我们精确高效地将多种iPSCs分化为下丘脑神经元,并利用复杂的基因表达和统计技术,证明了这些神经元与人类下丘脑组织相似。”

当然他也指出,要完全实现这一技术的功能,还需要更多的研究。

文章第一作者Uthra Rajamani博士也指出,这项研究的一个局限性在于,在体内特殊的下丘脑神经元也能与大脑其它中心相互交流,比如肠道,肝脏,胰腺等器官。这种系统性很难在培养皿中重现。

“未来,我们希望能分析iPSC产生的下丘脑神经元和其他相关细胞类型之间的功能交流,并在培养皿中创建相关的人体神经环路,这些神经元可以像在人体中一样与其他器官进行交流,”Rajamani说。

原始出处:Uthra Rajamani, Andrew R. Gross, Brooke E. Hjelm, et al. Super-Obese Patient-Derived iPSC Hypothalamic Neurons Exhibit Obesogenic Signatures and Hormone Responses. Cell Stem Cell. (2018)

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    2018-08-09 维他命
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  5. 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topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTKcmgibQ4oCrK7Z6f4CvMcs4k7QUGCkhopcGxvxaBfVciadECSIwaRVttllIOEKumpEaRrq5PoOUxow/0, createdBy=e3bb2081203, createdName=哈哈869, createdTime=Sat Apr 21 10:30:34 CST 2018, time=2018-04-21, status=1, ipAttribution=)]
    2018-04-26 海之蓝

    学习

    0

  6. 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    2018-04-23 溜溜梅不酸

    学习了.谢谢分享

    0

  7. 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    2018-04-23 小贝熊

    学习学习学习

    0

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    2018-04-21 哈哈869

    学了

    0

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