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Cell atlases visualized
追踪基因表达和染色质可用性的两种胎儿细胞壳种在此被视为地球的日夜和夜间。(认知工作室Inc.插图/ Dani Bergey)

两种新的人体细胞坦特拉斯已经绘制了概念后几周内构建组织的分子机械 - 并且最终可能指出到解决发育障碍的方式。

The researchers behind the atlases say their method for single-cell analysis, detailed in a pair of studies published by the journal Science, could dramatically accelerate efforts to trace how individual cells develop from the embryo to adulthood.

“关键是,该方法呈指数级级,”华盛顿遗传学大学说杰伊·桑德, a senior author for both studies. “When you think about the human body, there’s 37 trillion cells. To really get the kind of comprehensive atlases that we want, we want this kind of scalability.”

学习共同作者Dan Doherty是一位UW儿科教授,比较了该程序对哈勃太空望远镜或人类基因组项目的影响。“单细胞方法 - 难以估计他们对理解发展生物学的重要性,”他说。“他们真的给了我们一张我们以前从未见过的照片。”


One atlas focuses on gene expression在15种类型的胎儿组织中,从概念后10至18周的开发阶段。基因表达是指细胞中单个基因的方式打开或关闭以产生确定细胞结构和功能的蛋白质。




The researchers cataloged 77 main cell types, which could be further classified into 657 subtypes. Some of the main cell types were found in multiple tissue cells, but most of them were organ-specific. In some cases, the way that a cell developed depended on the kind of tissue where it was found.

“这可能与器官的组织特定功能”可能有关,“Shendure解释说。“在肺中,血管可能具有不同的原因或环境触发器,用于收缩或扩展 - 它们响应于不同氧水平的信号。如果你思考它,它会有意义。“狗万平台


Which regions of DNA are open or closed?

The companion atlas专注于治理遗传活动的另一个因素。一种称为染色质的物质对照染色体中的DNA如何包装 - 使一些延伸的DNA打开并可以通过读取指示的分子机械接触,同时保持其他延伸关闭和无法进入。

“学习染色质为您提供了一种感觉的细胞监管”语法“,”学习合作Darren Cusanovich., an alumnus of Shendure’s lab who is now a professor at the University of Arizona. “The short stretches of DNA that are open, or accessible, are enriched for certain ‘words,’ which are in turn the basis for the cell to specify that it wants certain genes on.”




uw postdoctoral cellowSilvia Domcke, one of the chromatin study’s lead authors, said the results can reveal which parts of the genome are functional even thoughthey don’t encode protein sequences



Shendure said the atlases are likely to improve our understanding of the machinery inside our cells, and how that machinery develops differently in different types of cells. That could bring new approaches to treating developmental disorders that are “individually rare but collectively common, and often devastating when they occur,” Shendure said.


Shendure said one potential frontier is known ascis-regulation therapy。该方法利用基因编辑工具,例如CRISPR,但扭曲。

“You’re using CRISPR not to target the gene, but to target the sequence that conveys the regulatory signal,” Shendure said. Cell atlases like the ones published today could identify new targets to go after.



One point of controversy has to do with the studies’ use of human fetal tissue. Samples were obtained from UW’s Birth Defects Research Laboratory, which自1964年以来一直存在。实验室运作a set of ethical guidelines drawn up by the National Institutes of Health但已经定期赶上在里面数十年长的争论堕胎

UW的Dan Doherty表示,对于细胞阿特拉斯项目和许多其他研究研究,组织样品一直是“令人难以置信的价值”。


Both single-cell atlases, plus other resources, are available online via a website at Seattle’s Brotman Baty Institute known as笛卡尔(或多或少地代表DEvelopmental.SingCell.A基因的TlasRegula.Tion andEXpre.SSion)。除了在UW的帖子外,Shendure是Brotman Baty Institute的科学主任。

来自UW医学,Brotman Baty Institute,Illumina,亚利桑那大学,Max Planck分子遗传学研究所和罗彻斯特大学医学中心的弗雷迪纳大学的Brotman Baty Institute,Max Planck Medical Center大学的Batrumina。研究的组成部分由布罗特曼Baty Institute,Paul G. Allen Frientiers基金会,Chan Zuckerberg倡议,Howard Hughes医学研究所和国家健康研究院提供资金。