小柯机器人

近日，美国加州大学圣迭戈分校任兵等研究人员合作揭示哺乳动物新皮层基因调控程序的保守与分化。2023年12月13日，《自然》杂志在线发表了这项成果。

研究人员使用单细胞多组学检测方法研究了人类、猕猴、狨猴和小鼠初级运动皮层的基因调控程序，从总共超过20万个细胞中生成了基因表达、染色质可及性、DNA甲基组和染色体构象图谱。从这些数据中，研究人员发现转录因子表达的差异与物种特有的表观基因组景观相对应。研究人员发现，基因调控特征的保守性和差异性反映在三维基因组的演化中。可转座元件占大脑皮层细胞中人类特异性候选顺式调控元件的近80%。

通过机器学习，研究人员开发了不同物种中基于序列的候选顺式调控元件预测器，并证明从啮齿动物到灵长类动物，基因组调控句法高度保守。最后，研究人员证明了表观遗传学保护与序列相似性相结合有助于发现功能性顺式调控元件，并提高人们解释导致神经系统疾病和性状的基因变异的能力。

据介绍，顺式调控元件的分化驱动了物种特异性，但这种分化在分子和细胞水平上如何体现在新皮层的演化中仍不清楚。

附：英文原文

Title: Conserved and divergent gene regulatory programs of the mammalian neocortex

Author: Zemke, Nathan R., Armand, Ethan J., Wang, Wenliang, Lee, Seoyeon, Zhou, Jingtian, Li, Yang Eric, Liu, Hanqing, Tian, Wei, Nery, Joseph R., Castanon, Rosa G., Bartlett, Anna, Osteen, Julia K., Li, Daofeng, Zhuo, Xiaoyu, Xu, Vincent, Chang, Lei, Dong, Keyi, Indralingam, Hannah S., Rink, Jonathan A., Xie, Yang, Miller, Michael, Krienen, Fenna M., Zhang, Qiangge, Taskin, Naz, Ting, Jonathan, Feng, Guoping, McCarroll, Steven A., Callaway, Edward M., Wang, Ting, Lein, Ed S., Behrens, M. Margarita, Ecker, Joseph R., Ren, Bing

Issue&Volume: 2023-12-13

Abstract: Divergence of cis-regulatory elements drives species-specific traits1, but how this manifests in the evolution of the neocortex at the molecular and cellular level remains unclear. Here we investigated the gene regulatory programs in the primary motor cortex of human, macaque, marmoset and mouse using single-cell multiomics assays, generating gene expression, chromatin accessibility, DNA methylome and chromosomal conformation profiles from a total of over 200,000 cells. From these data, we show evidence that divergence of transcription factor expression corresponds to species-specific epigenome landscapes. We find that conserved and divergent gene regulatory features are reflected in the evolution of the three-dimensional genome. Transposable elements contribute to nearly 80% of the human-specific candidate cis-regulatory elements in cortical cells. Through machine learning, we develop sequence-based predictors of candidate cis-regulatory elements in different species and demonstrate that the genomic regulatory syntax is highly preserved from rodents to primates. Finally, we show that epigenetic conservation combined with sequence similarity helps to uncover functional cis-regulatory elements and enhances our ability to interpret genetic variants contributing to neurological disease and traits.

DOI: 10.1038/s41586-023-06819-6

Source: https://www.nature.com/articles/s41586-023-06819-6

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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