生物
转录组
基因组
染色质
染色体构象捕获
计算生物学
基因
基因表达
遗传学
增强子
作者
Longzhi Tan,Wenping Ma,Honggui Wu,Yao Zheng,Dong Xing,Ritchie Chen,Xiang Li,Nicholas Daley,Karl Deisseroth,X. Sunney Xie
出处
期刊:Cell
[Elsevier]
日期:2021-02-01
卷期号:184 (3): 741-758.e17
被引量:115
标识
DOI:10.1016/j.cell.2020.12.032
摘要
Both transcription and three-dimensional (3D) architecture of the mammalian genome play critical roles in neurodevelopment and its disorders. However, 3D genome structures of single brain cells have not been solved; little is known about the dynamics of single-cell transcriptome and 3D genome after birth. Here, we generated a transcriptome (3,517 cells) and 3D genome (3,646 cells) atlas of the developing mouse cortex and hippocampus by using our high-resolution multiple annealing and looping-based amplification cycles for digital transcriptomics (MALBAC-DT) and diploid chromatin conformation capture (Dip-C) methods and developing multi-omic analysis pipelines. In adults, 3D genome “structure types” delineate all major cell types, with high correlation between chromatin A/B compartments and gene expression. During development, both transcriptome and 3D genome are extensively transformed in the first post-natal month. In neurons, 3D genome is rewired across scales, correlated with gene expression modules, and independent of sensory experience. Finally, we examine allele-specific structure of imprinted genes, revealing local and chromosome (chr)-wide differences. These findings uncover an unknown dimension of neurodevelopment.
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