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“剪出”人类灭绝近亲的迷你大脑—论文—科学网

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Trujillo 来源:《科学》 发布时间:2021/2/17 16:15:19</div> <div style="height: 20px; margin: 0 auto; border-bottom: solid 1px #bbc89b; margin-top: 10px; width: 18%; font: 12px 宋体; float: right"> 选择字号:<span onclick="showsize(12)" style="background-color: #587c19; color: #fff; font-size: 12px; cursor: pointer">小</span> <span onclick="showsize(14)" style="background-color: #587c19; color: #fff; font-size: 12px; cursor: pointer">中</span> <span onclick="showsize(16)" style="background-color: #587c19; color: #fff; font-size: 12px; cursor: pointer"> 大</span> </div> </td> </tr> <tr> <td> <div id="content1" style="width: 94%; font: 14px 宋体; text-align: left; line-height: 24px; word-wrap: break-word"> <table width="100%" border="0" cellspacing="0" cellpadding="0"> <tr> <td height="20"> </td> </tr> <tr> <td align="center" valign="middle" class="style1" style="font-size: 13px; color: #333333; font-family: 宋体; line-height: 20px"> <b></b></td> </tr> <tr> <td align="center" class="style1" style="font-size: 22px; color: #587c19; font-family: 黑体; line-height: 30px"> “剪出”人类灭绝近亲的迷你大脑</td> </tr> <tr> <td align="center" valign="middle" class="style1" style="font-size: 13px; color: #333333; font-family: 宋体; line-height: 20px;"> <b></b></td> </tr> </table> <p> &nbsp;</p> <p style="text-align:center;"> <img src="/upload/news/images/2021/2/202121714393417.jpg" /></p> <p style="text-align: center;"> &nbsp;<strong>研究人员在实验室培养大脑类器官艺术图&nbsp; &nbsp;图片来源:Fabio Buonocore</strong></p> <p style="text-indent:2em"> 研究人员创造了一种小型类脑器官,其含有两种灭绝的人类近亲&mdash;&mdash;尼安德特人和丹尼索瓦人的基因变体。虽然,这些由人体干细胞制成的组织,远不能真正代表这些灭绝物种的大脑,但它们的大小、形状和纹理与人类类器官明显不同。相关论文近日刊登于《科学》,该成果有助于科学家理解人类大脑进化的基因路径。</p> <p style="text-indent:2em"> 瑞士巴塞尔大学发育生物学家Gray Camp表示,&ldquo;这是一篇非同寻常的论文,包含了一些非同寻常的观点。&rdquo;Camp实验室去年报告了正在生长的大脑类器官,其中含有尼安德特人和人类共有的一种基因。</p> <p style="text-indent:2em"> 人类与尼安德特人和丹尼索瓦人的关系比与任何现存的灵长类动物的关系都密切,而且,尼安德特人40%的基因组仍然存在人类身上。但是科学家研究这些古老物种大脑的手段有限&mdash;&mdash;软组织没有得到很好的保存,而且大多数研究依赖于检查头骨化石的大小和形状。了解这两种古人的基因与人类的不同是很重要的,因为它有助于研究人员理解是什么使人类独一无二&mdash;&mdash;尤其是在大脑中。</p> <p style="text-indent:2em"> 美国加州大学圣迭戈分校神经科学家Alysson Muotri团队利用基因编辑技术CRISPR-Cas9,将尼安德特人和丹尼索瓦人的NOVA1基因导入人类多能干细胞。他们将这些细胞培养成类器官&mdash;&mdash;类脑组织块,直径可达5毫米,并与正常的人类大脑类器官进行比较。</p> <p style="text-indent:2em"> 很明显,表达NOVA1古老变体的类器官是不同的。Muotri说:&ldquo;当看到类器官的形状时,我们就知道自己找到了一些东西。&rdquo;人类大脑的类器官通常是光滑和球形的,而古老基因类器官有粗糙、复杂的表面,而且更小。研究人员认为,这可能是由于细胞生长和繁殖方式的不同。</p> <p style="text-indent:2em"> 为确定在这些类器官中表达哪种古老基因,研究人员将人类基因组序列与两个尼安德特人和一个丹尼索瓦人的几乎完整的基因组进行了比较。他们发现了61种基因的人类版本与古老版本不同。其中,NOVA1参与形成大脑的突触或神经连接,当其活动改变时,就与神经紊乱有关。</p> <p style="text-indent:2em"> 人类NOVA1基因与其他现存灵长类动物的古老变体的区别仅在于一个碱基,研究人员使用CRISPR-Cas9将其编辑到干细胞中,并交换了由古老类有机物产生的NOVA1蛋白中的一个氨基酸。&ldquo;事实上,几乎所有人,现在都有这个版本,而不是旧版本,这意味着它在进化的某些阶段给了我们巨大的优势。现在的问题是,这些优势是什么?&rdquo;Muotri说。</p> <p style="text-indent:2em"> 研究小组发现,古老基因和人类类器官有277个基因具有不同的活性,已知其中一些基因会影响神经元的发育和连通性。这些古老类器官中确实含有不同水平的突触蛋白,它们的神经元活性比对照组的神经元更不规律,而且它们成熟得更快。</p> <p style="text-indent:2em"> 未参与该研究的德国慕尼黑路德维希&middot;马克西米利安大学进化遗传学家Wolfgang Enard说:&ldquo;最重要的发现是,将(基因)恢复到祖先的状态,你就会在有机体中看到一种效果。&rdquo;他对如此小的基因差异导致如此明显的变化感到惊讶,但他怀疑类器官的奇怪外观能否告诉我们很多关于尼安德特人大脑的信息。</p> <p style="text-indent:2em"> Camp也警告说,这些古老类器官不太可能完全代表真正的尼安德特人组织。相反,观察到的特征可能是改变了一种存在于人体的重要蛋白质的结果,因为随着时间的推移,许多突变叠加在一起产生了复合效应。他说:&ldquo;你把氨基酸拿掉,大脑就不能工作了。&rdquo;</p> <p style="text-indent:2em"> 也有专家认为,这种经过编辑的有机体方法对于研究灵长类动物的大脑进化还是有用的。Muotri团队计划将其他基因编辑到类器官中,从而为了解人类大脑提供思路。他说,如果研究人员能够理解将人类带入目前状态的进化途径,他们可能会加深对人类大脑特有疾病的理解。(来源:中国科学报&nbsp;鲁亦)</p> <p style="text-indent:2em"> 相关论文信息:<a href="https://doi.org/10.1126/science.aax2537" target="_blank">https://doi.org/10.1126/science.aax2537</a></p> <p style="text-indent: 2em;"> &nbsp;</p> <div> &nbsp;</div> <div class="bq" style="text-indent:0em;font-weight:bold;font-size:13px;border:solid 1px #333 ;padding:10px;"> 版权声明:凡本网注明&ldquo;来源:中国科学报、科学网、科学新闻杂志&rdquo;的所有作品,网站转载,请在正文上方注明来源和作者,且不得对内容作实质性改动;微信公众号、头条号等新媒体平台,转载请联系授权。邮箱:shouquan@stimes.cn。</div> <div style="border-bottom: solid 1px #bfc89d; 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