Evolution of regulatory signatures in primate cortical neurons at cell-type resolution.
Evolution of regulatory signatures in primate cortical neurons at cell-type resolution.
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DOI：
10.1073/pnas.2011884117
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发表时间：
2020-11-10
影响因子：
11.1
通讯作者：
Dracheva S
中科院分区：
文献类型：
--
作者：
Kozlenkov A;Vermunt MW;Apontes P;Li J;Hao K;Sherwood CC;Hof PR;Ely JJ;Wegner M;Mukamel EA;Creyghton MP;Koonin EV;Dracheva S
人类大脑的大脑皮层是一种高度复杂的异质组织，包含许多细胞类型，这些细胞类型在基因表达水平上受到非编码调控元件的精细调控，可能是以细胞类型依赖性方式。然而，评估单个细胞类型中的调控元件在技术上具有挑战性，因此大多数先前关于基因调控的研究都是用大块脑组织进行的。在这里，我们分析了两种主要类型的神经元分离的大脑皮层的人类，黑猩猩，猕猴，并报告复杂的模式的细胞类型特异性进化的调控元件在许多基因。许多具有进化调节的基因与语言能力和精神疾病有关。人类大脑皮层包含许多细胞类型，这些细胞在进化过程中可能经历了独立的功能变化。然而，皮质中的细胞类型特异性调控景观在很大程度上仍未被探索。在这里，我们报告了两个主要的皮质神经元亚型，多巴胺能投射神经元和GABA能中间神经元，在人类，黑猩猩，恒河猴的表观基因组和转录组学分析。使用全基因组分析的H3K27ac组蛋白修饰，我们确定了神经元亚型特异性的调控元件，以前在散装脑组织样本中未检测到。在多个基因中发现了人类特有的调控变化，包括与语言，自闭症谱系障碍和药物成瘾相关的基因。我们观察到优先的神经元亚型特异性调控元件的进化趋异，并表明相当一部分泛神经元调控元件经历亚型特异性的进化变化。这项研究揭示了调控进化和细胞类型依赖的基因表达程序之间的相互作用，并为进一步探索人类大脑的进化和功能提供了资源。
The cerebral cortex of the human brain is a highly complex, heterogeneous tissue that contains many cell types that are exquisitely regulated at the level of gene expression by noncoding regulatory elements, presumably in a cell-type–dependent manner. However, assessing the regulatory elements in individual cell types is technically challenging, and therefore most of the previous studies on gene regulation were performed with bulk brain tissue. Here we analyze two major types of neurons isolated from the cerebral cortex of humans, chimpanzees, and rhesus macaques, and report complex patterns of cell-type–specific evolution of the regulatory elements in numerous genes. Many genes with evolving regulation are implicated in language abilities as well as psychiatric disorders. The human cerebral cortex contains many cell types that likely underwent independent functional changes during evolution. However, cell-type–specific regulatory landscapes in the cortex remain largely unexplored. Here we report epigenomic and transcriptomic analyses of the two main cortical neuronal subtypes, glutamatergic projection neurons and GABAergic interneurons, in human, chimpanzee, and rhesus macaque. Using genome-wide profiling of the H3K27ac histone modification, we identify neuron-subtype–specific regulatory elements that previously went undetected in bulk brain tissue samples. Human-specific regulatory changes are uncovered in multiple genes, including those associated with language, autism spectrum disorder, and drug addiction. We observe preferential evolutionary divergence in neuron subtype-specific regulatory elements and show that a substantial fraction of pan-neuronal regulatory elements undergoes subtype-specific evolutionary changes. This study sheds light on the interplay between regulatory evolution and cell-type–dependent gene-expression programs, and provides a resource for further exploration of human brain evolution and function.
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影响因子：
25
作者：
Chen, Yi-Chuan;Kuo, Hsiao-Ying;Bornschein, Ulrich;Takahashi, Hiroshi;Chen, Shih-Yun;Lu, Kuan-Ming;Yang, Hao-Yu;Chen, Gui-May;Lin, Jing-Ruei;Lee, Yi-Hsin;Chou, Yun-Chia;Cheng, Sin-Jhong;Chien, Cheng-Ting;Enard, Wolfgang;Hevers, Wulf;Paeaebo, Svante;Graybiel, Ann M.;Liu, Fu-Chin
通讯作者：
Liu, Fu-Chin
人类肌肉和大脑代谢组的异常进化差异与人类认知和身体独特性相似
影响因子：
9.8
作者：
Bozek K;Wei Y;Yan Z;Liu X;Xiong J;Sugimoto M;Tomita M;Pääbo S;Pieszek R;Sherwood CC;Hof PR;Ely JJ;Steinhauser D;Willmitzer L;Bangsbo J;Hansson O;Call J;Giavalisco P;Khaitovich P
通讯作者：
Khaitovich P
影响因子：
30.8
作者：
Grosselin, Kevin;Durand, Adeline;Gerard, Annabelle
通讯作者：
Gerard, Annabelle
影响因子：
16.6
作者：
Castelijns, Bas;Baak, Mirna L.;Creyghton, Menno P.
通讯作者：
Creyghton, Menno P.
影响因子：
10.6
作者：
Hancock DB;Levy JL;Gaddis NC;Glasheen C;Saccone NL;Page GP;Hulse GK;Wildenauer D;Kelty EA;Schwab SG;Degenhardt L;Martin NG;Montgomery GW;Attia J;Holliday EG;McEvoy M;Scott RJ;Bierut LJ;Nelson EC;Kral AH;Johnson EO
通讯作者：
Johnson EO