Single-cell multiplex chromatin and RNA interactions in aging human brain.
Single-cell multiplex chromatin and RNA interactions in aging human brain.
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衰老人脑中单细胞多重染色质和 RNA 相互作用。
DOI：
10.1101/2023.06.28.546457
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Zhong,Sheng
中科院分区：
文献类型：
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作者：
Wen,Xingzhao;Luo,Zhifei;Zhao,Wenxin;Calandrelli,Riccardo;Nguyen,TriC;Wan,Xueyi;Richard,JohnLalithCharles;Zhong,Sheng
动态组织的染色质复合物往往涉及多重染色质相互作用，有时染色质相关的RNA，-。染色质复合物的组成在细胞分化和衰老过程中发生变化，并且预期在终末分化的单细胞中是高度异质的。在这里，我们介绍了多核酸相互作用映射在单细胞（MUSIC）技术的并发分析的多重染色质相互作用，基因表达和RNA染色质协会在个别核。当应用于14个来自老年捐赠者的人类额叶皮层样本时，MUSIC描绘了不同的皮层细胞类型和状态。我们观察到，细胞核表现出更少的短程染色质相互作用与“老年人”转录组签名和阿尔茨海默病病理学相关。此外，在表达数量性状基因座和启动子之间表现出染色质接触的细胞类型倾向于其中这些表达数量性状基因座特异性地影响其靶基因的表达。此外，女性皮质细胞表现出XIST非编码RNA和X染色体之间的高度异质性相互作用，沿着X染色体的不同空间组织。MUSIC为复杂组织中细胞分辨率下的染色质结构和转录的探索提供了有力的工具。
Dynamically organized chromatin complexes often involve multiplex chromatin interactions and sometimes chromatin-associated RNA, –. Chromatin complex compositions change during cellular differentiation and ageing, and are expected to be highly heterogeneous among terminally differentiated single cells, , –. Here we introduce the multinucleic acid interaction mapping in single cells (MUSIC) technique for concurrent profiling of multiplex chromatin interactions, gene expression and RNA–chromatin associations within individual nuclei. When applied to 14 human frontal cortex samples from older donors, MUSIC delineated diverse cortical cell types and states. We observed that nuclei exhibiting fewer short-range chromatin interactions were correlated with both an ‘older’ transcriptomic signature and Alzheimer’s disease pathology. Furthermore, the cell type exhibiting chromatin contacts betweencisexpression quantitative trait loci and a promoter tends to be that in which thesecisexpression quantitative trait loci specifically affect the expression of their target gene. In addition, female cortical cells exhibit highly heterogeneous interactions between XIST non-coding RNA and chromosome X, along with diverse spatial organizations of the X chromosomes. MUSIC presents a potent tool for exploration of chromatin architecture and transcription at cellular resolution in complex tissues.