Changes in genome architecture and transcriptional dynamics progress independently of sensory experience during post-natal brain development
Changes in genome architecture and transcriptional dynamics progress independently of sensory experience during post-natal brain development
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DOI：
10.1016/j.cell.2020.12.032
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发表时间：
2021-02-04
期刊：
影响因子：
64.5
通讯作者：
Xie, X. Sunney
中科院分区：
文献类型：
--
作者：
Tan, Longzhi;Ma, Wenping;Xie, X. Sunney
哺乳动物基因组的转录和三维（3D）结构在神经发育及其疾病中起着关键作用。然而，单个脑细胞的3D基因组结构尚未解决;对出生后单细胞转录组和3D基因组的动态知之甚少。在这里，我们通过使用我们的高分辨率多重退火和基于环的扩增循环的数字转录组学（MALBAC-DT）和二倍体染色质构象捕获（Dip-C）方法以及开发多组学分析管道，生成了发育中小鼠皮层和海马的转录组（3，517个细胞）和3D基因组（3，646个细胞）图谱。在成人中，3D基因组“结构类型”描绘了所有主要细胞类型，染色质A/B区室与基因表达之间具有高度相关性。在发育过程中，转录组和3D基因组都在出生后的第一个月内发生了广泛的转变。在神经元中，3D基因组跨尺度重新连接，与基因表达模块相关，并且独立于感官体验。最后，我们研究了印记基因的等位基因特异性结构，揭示了局部和染色体（chr）范围内的差异。这些发现揭示了神经发育的一个未知维度。
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.