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An atlas of cortical arealization identifies dynamic molecular signatures

机译：皮质体积化图集鉴定动态分子签名

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摘要

The human brain is subdivided into distinct anatomical structures, including the neocortex, which in turn encompasses dozens of distinct specialized cortical areas. Early morphogenetic gradients are known to establish early brain regions and cortical areas, but how early patterns result in finer and more discrete spatial differences remains poorly understood~(1). Here we use single-cell RNA sequencing to profile ten major brain structures and six neocortical areas during peak neurogenesis and early gliogenesis. Within the neocortex, we find that early in the second trimester, a large number of genes are differentially expressed across distinct cortical areas in all cell types, including radial glia, the neural progenitors of the cortex. However, the abundance of areal transcriptomic signatures increases as radial glia differentiate into intermediate progenitor cells and ultimately give rise to excitatory neurons. Using an automated, multiplexed single-molecule fluorescent in situ hybridization approach, we find that laminar gene-expression patterns are highly dynamic across cortical regions. Together, our data suggest that early cortical areal patterning is defined by strong, mutually exclusive frontal and occipital gene-expression signatures, with resulting gradients giving rise to the specification of areas between these two poles throughout successive developmental timepoints.
机译：人脑被细分为不同的解剖结构，包括Neocortex，这又包括数十种不同的专业皮质区域。已知早期的形态发生梯度建立早期的脑区和皮质区域，但如何早期模式导致更精细，更离的空间差异仍然是〜（1）。在这里，我们在峰神经发生期间使用单细胞RNA测序来概况十个主要脑结构和六个新奇区域。在Neocortex中，我们发现，在第二个三个月的早期，大量基因在所有细胞类型中的不同皮质区域差异表达，包括径向胶质胶质，皮质的神经祖细胞。然而，由于径向胶质胶质胶质细胞分化为中介祖细胞并最终导致兴奋性神经元，因此产生的体转录组签名的丰度增加。使用自动化的多重单分子荧光原位杂交方法，我们发现层层基因表达模式跨皮质区域高度动态。我们的数据表明，早期皮质面积图案化由强烈，相互专有的正面和枕部基因表达签名定义，产生的梯度导致在连续发育时间点的整个两极之间的区域之间的规范。

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  • 来源
    《Nature》 |2021年第7879期|200-204|共5页
  • 作者

    Aparna Bhaduri; Carmen Sandoval-Espinosa; Marcos Otero-Garcia; Irene Oh; Raymund Yin; Ugomma C Eze; Tomasz J Nowakowski; Arnold R Kriegstein;

  • 作者单位

    Department of Neurology University of California|The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research University of California|Department of Biological Chemistry;

    Department of Neurology University of California|The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research University of California;

    Rebus Biosystems;

    Rebus Biosystems;

    Rebus Biosystems;

    Department of Neurology University of California|The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research University of California;

    Department of Neurology University of California|Department of Anatomy University of California;

    Department of Neurology University of California|The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research University of California;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 正文语种 eng
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