Single-cell analysis of chromatin accessibility in the adult mouse brain.
Single-cell analysis of chromatin accessibility in the adult mouse brain.
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DOI：
10.1038/s41586-023-06824-9
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发表时间：
2023-12
期刊：
影响因子：
64.8
通讯作者：
Ren, Bing
中科院分区：
文献类型：
--
作者：
Zu, Songpeng;Li, Yang Eric;Wang, Kangli;Armand, Ethan J.;Mamde, Sainath;Amaral, Maria Luisa;Wang, Yuelai;Chu, Andre;Xie, Yang;Miller, Michael;Xu, Jie;Wang, Zhaoning;Zhang, Kai;Jia, Bojing;Hou, Xiaomeng;Lin, Lin;Yang, Qian;Lee, Seoyeon;Li, Bin;Kuan, Samantha;Liu, Hanqing;Zhou, Jingtian;Pinto-Duarte, Antonio;Lucero, Jacinta;Osteen, Julia;Nunn, Michael;Smith, Kimberly A.;Tasic, Bosiljka;Yao, Zizhen;Zeng, Hongkui;Wang, Zihan;Shang, Jingbo;Behrens, M. Margarita;Ecker, Joseph R.;Wang, Allen;Preissl, Sebastian;Ren, Bing
单细胞技术的最新进展已经发现了数千种脑细胞类型;然而，我们对这些细胞类型中基因调控程序的理解还远未完成。在这里，我们报告了一个全面的图集候选顺式调控DNA元件（cCREs）在成年小鼠大脑中，通过分析染色质的可及性在230万个脑细胞从117解剖。该图谱包括约100万个cCREs及其在1，482个不同脑细胞群体中的染色质可及性，为小鼠基因组中最近的此类注释增加了超过446，000个cCREs。小鼠脑cCREs在人脑中适度保守。小鼠特异性的cCREs，特别是从一个子集的皮质兴奋性神经元，是非常丰富的转座因子，这表明转座因子在出现新的监管程序和神经元多样性的潜在作用。最后，我们推断了260多个小鼠脑细胞亚类中的基因调控网络，并开发了深度学习模型，仅从DNA序列预测不同脑细胞类型中基因调控元件的活动。我们的研究结果为分析小鼠和人脑中细胞类型特异性基因调控程序提供了资源。成年小鼠大脑中候选顺式调控DNA元件（cCREs）的图谱揭示了驱动大脑结构和功能异质性和复杂性的转录调控程序。
Recent advances in single-cell technologies have led to the discovery of thousands of brain cell types; however, our understanding of the gene regulatory programs in these cell types is far from complete. Here we report a comprehensive atlas of candidate cis-regulatory DNA elements (cCREs) in the adult mouse brain, generated by analysing chromatin accessibility in 2.3 million individual brain cells from 117 anatomical dissections. The atlas includes approximately 1 million cCREs and their chromatin accessibility across 1,482 distinct brain cell populations, adding over 446,000 cCREs to the most recent such annotation in the mouse genome. The mouse brain cCREs are moderately conserved in the human brain. The mouse-specific cCREs—specifically, those identified from a subset of cortical excitatory neurons—are strongly enriched for transposable elements, suggesting a potential role for transposable elements in the emergence of new regulatory programs and neuronal diversity. Finally, we infer the gene regulatory networks in over 260 subclasses of mouse brain cells and develop deep-learning models to predict the activities of gene regulatory elements in different brain cell types from the DNA sequence alone. Our results provide a resource for the analysis of cell-type-specific gene regulation programs in both mouse and human brains. An atlas of candidate cis-regulatory DNA elements (cCREs) in the adult mouse brain unravels the transcriptional regulatory programs that drive the heterogeneity and complexity of brain structure and function.
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影响因子：
9.8
作者：
ENCODE Project Consortium
通讯作者：
ENCODE Project Consortium
影响因子：
64.8
作者：
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通讯作者：
Shendure, Jay
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作者：
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作者：
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