• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

衰老人类大脑中的单细胞多重染色质与RNA相互作用

Single-cell multiplex chromatin and RNA interactions in aging human brain.

作者信息

Wen Xingzhao, Luo Zhifei, Zhao Wenxin, Calandrelli Riccardo, Nguyen Tri C, Wan Xueyi, Richard John Lalith Charles, Zhong Sheng

机构信息

Program in Bioinformatics and Systems Biology, University of California San Diego, La Jolla, CA 92093, USA.

Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA.

出版信息

bioRxiv. 2024 Mar 4:2023.06.28.546457. doi: 10.1101/2023.06.28.546457.

DOI:10.1101/2023.06.28.546457
PMID:37425846
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10326989/
Abstract

The dynamically organized chromatin complexes often involve multiplex chromatin interactions and sometimes chromatin-associated RNA (caRNA) . Chromatin complex compositions change during cellular differentiation and aging, and are expected to be highly heterogeneous among terminally differentiated single cells . Here we introduce the Multi-Nucleic Acid Interaction Mapping in Single Cell (MUSIC) technique for concurrent profiling of multiplex chromatin interactions, gene expression, and RNA-chromatin associations within individual nuclei. Applied to 14 human frontal cortex samples from elderly donors, MUSIC delineates diverse cortical cell types and states. We observed the nuclei exhibiting fewer short-range chromatin interactions are correlated with an "older" transcriptomic signature and with Alzheimer's pathology. Furthermore, the cell type exhibiting chromatin contacts between cis expression quantitative trait loci (cis eQTLs) and a promoter tends to be the cell type where these cis eQTLs specifically affect their target gene's expression. Additionally, the female cortical cells exhibit highly heterogeneous interactions between the XIST non-coding RNA and Chromosome X, along with diverse spatial organizations of the X chromosomes. MUSIC presents a potent tool for exploring chromatin architecture and transcription at cellular resolution in complex tissues.

摘要

动态组织的染色质复合物通常涉及多重染色质相互作用，有时还涉及染色质相关RNA（caRNA）。染色质复合物的组成在细胞分化和衰老过程中会发生变化，并且在终末分化的单细胞之间预计具有高度异质性。在这里，我们介绍了单细胞多核酸相互作用图谱（MUSIC）技术，用于同时分析单个细胞核内的多重染色质相互作用、基因表达和RNA-染色质关联。将MUSIC应用于来自老年供体的14个人类额叶皮质样本，它描绘了不同的皮质细胞类型和状态。我们观察到，短程染色质相互作用较少的细胞核与“衰老”的转录组特征以及阿尔茨海默病病理学相关。此外，在顺式表达定量性状位点（cis eQTLs）和启动子之间表现出染色质接触的细胞类型往往是这些顺式eQTLs特异性影响其靶基因表达的细胞类型。此外，雌性皮质细胞在XIST非编码RNA和X染色体之间表现出高度异质的相互作用，以及X染色体的不同空间组织。MUSIC为在复杂组织中以细胞分辨率探索染色质结构和转录提供了一个强大的工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5925/10913971/75910df07b84/nihpp-2023.06.28.546457v2-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5925/10913971/22c088a03a09/nihpp-2023.06.28.546457v2-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5925/10913971/685c845e2121/nihpp-2023.06.28.546457v2-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5925/10913971/ea304ca4c4f5/nihpp-2023.06.28.546457v2-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5925/10913971/4854d127a7d5/nihpp-2023.06.28.546457v2-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5925/10913971/507f4ca70bcc/nihpp-2023.06.28.546457v2-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5925/10913971/1029fcfe8032/nihpp-2023.06.28.546457v2-f0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5925/10913971/fa1a2c055468/nihpp-2023.06.28.546457v2-f0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5925/10913971/46de86265fb6/nihpp-2023.06.28.546457v2-f0012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5925/10913971/767f9ae101ec/nihpp-2023.06.28.546457v2-f0013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5925/10913971/57122a30a7f9/nihpp-2023.06.28.546457v2-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5925/10913971/75910df07b84/nihpp-2023.06.28.546457v2-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5925/10913971/22c088a03a09/nihpp-2023.06.28.546457v2-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5925/10913971/685c845e2121/nihpp-2023.06.28.546457v2-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5925/10913971/ea304ca4c4f5/nihpp-2023.06.28.546457v2-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5925/10913971/4854d127a7d5/nihpp-2023.06.28.546457v2-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5925/10913971/507f4ca70bcc/nihpp-2023.06.28.546457v2-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5925/10913971/1029fcfe8032/nihpp-2023.06.28.546457v2-f0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5925/10913971/fa1a2c055468/nihpp-2023.06.28.546457v2-f0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5925/10913971/46de86265fb6/nihpp-2023.06.28.546457v2-f0012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5925/10913971/767f9ae101ec/nihpp-2023.06.28.546457v2-f0013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5925/10913971/57122a30a7f9/nihpp-2023.06.28.546457v2-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5925/10913971/75910df07b84/nihpp-2023.06.28.546457v2-f0002.jpg

相似文献

1
Single-cell multiplex chromatin and RNA interactions in aging human brain.衰老人类大脑中的单细胞多重染色质与RNA相互作用
bioRxiv. 2024 Mar 4:2023.06.28.546457. doi: 10.1101/2023.06.28.546457.
2
Single-cell multiplex chromatin and RNA interactions in ageing human brain.单细胞多重染色质和 RNA 相互作用在衰老人类大脑中的研究。
Nature. 2024 Apr;628(8008):648-656. doi: 10.1038/s41586-024-07239-w. Epub 2024 Mar 27.
3
Integrative modeling of eQTLs and cis-regulatory elements suggests mechanisms underlying cell type specificity of eQTLs.整合 eQTL 和顺式调控元件的建模提示了 eQTL 细胞类型特异性的潜在机制。
PLoS Genet. 2013;9(8):e1003649. doi: 10.1371/journal.pgen.1003649. Epub 2013 Aug 1.
4
Whole-organism eQTL mapping at cellular resolution with single-cell sequencing.单细胞测序实现细胞分辨率的全器官 eQTL 图谱绘制。
Elife. 2021 Mar 18;10:e65857. doi: 10.7554/eLife.65857.
5
Joint analyses of multi-tissue Hi-C and eQTL data demonstrate close spatial proximity between eQTLs and their target genes.联合分析多组织 Hi-C 和 eQTL 数据表明，eQTL 与其靶基因之间具有密切的空间临近性。
BMC Genet. 2019 Apr 30;20(1):43. doi: 10.1186/s12863-019-0744-x.
6
Spen links RNA-mediated endogenous retrovirus silencing and X chromosome inactivation.Spen 连接 RNA 介导的内源性逆转录病毒沉默和 X 染色体失活。
Elife. 2020 May 7;9:e54508. doi: 10.7554/eLife.54508.
7
Enhancer variants associated with Alzheimer's disease affect gene expression via chromatin looping.与阿尔茨海默病相关的增强子变异通过染色质环影响基因表达。
BMC Med Genomics. 2019 Sep 9;12(1):128. doi: 10.1186/s12920-019-0574-8.
8
A global high-density chromatin interaction network reveals functional long-range and trans-chromosomal relationships.一个全球性的高密度染色质相互作用网络揭示了功能上的长程和跨染色体关系。
Genome Biol. 2022 Nov 9;23(1):238. doi: 10.1186/s13059-022-02790-z.
9
Familial cases of point mutations in the XIST promoter reveal a correlation between CTCF binding and pre-emptive choices of X chromosome inactivation.XIST启动子点突变的家族性病例揭示了CTCF结合与X染色体失活的优先选择之间的相关性。
Hum Mol Genet. 2005 Apr 1;14(7):953-65. doi: 10.1093/hmg/ddi089. Epub 2005 Feb 24.
10
Single-nucleus chromatin accessibility and transcriptomic characterization of Alzheimer's disease.阿尔茨海默病中单细胞核染色质可及性和转录组特征。
Nat Genet. 2021 Aug;53(8):1143-1155. doi: 10.1038/s41588-021-00894-z. Epub 2021 Jul 8.

本文引用的文献

1
Cooltools: Enabling high-resolution Hi-C analysis in Python.酷工具：在 Python 中实现高分辨率 Hi-C 分析。
PLoS Comput Biol. 2024 May 6;20(5):e1012067. doi: 10.1371/journal.pcbi.1012067. eCollection 2024 May.
2
Genome-wide analysis of the interplay between chromatin-associated RNA and 3D genome organization in human cells.人类细胞中染色质相关 RNA 与 3D 基因组组织相互作用的全基因组分析。
Nat Commun. 2023 Oct 16;14(1):6519. doi: 10.1038/s41467-023-42274-7.
3
Epigenomic dissection of Alzheimer's disease pinpoints causal variants and reveals epigenome erosion.
阿尔茨海默病的表观基因组剖析确定了因果变异，并揭示了表观基因组的侵蚀。
Cell. 2023 Sep 28;186(20):4422-4437.e21. doi: 10.1016/j.cell.2023.08.040.
4
Lifelong restructuring of 3D genome architecture in cerebellar granule cells.小脑颗粒细胞中 3D 基因组结构的终身重构。
Science. 2023 Sep 8;381(6662):1112-1119. doi: 10.1126/science.adh3253. Epub 2023 Sep 7.
5
A transcriptome-based single-cell biological age model and resource for tissue-specific aging measures.基于转录组的单细胞生物年龄模型和组织特异性衰老测量资源。
Genome Res. 2023 Aug;33(8):1381-1394. doi: 10.1101/gr.277491.122. Epub 2023 Jul 31.
6
Linking genome structures to functions by simultaneous single-cell Hi-C and RNA-seq.通过单细胞 Hi-C 和 RNA-seq 同时将基因组结构与功能联系起来。
Science. 2023 Jun 9;380(6649):1070-1076. doi: 10.1126/science.adg3797. Epub 2023 Jun 8.
7
Myelin dysfunction drives amyloid-β deposition in models of Alzheimer's disease.髓鞘功能障碍导致阿尔茨海默病模型中的淀粉样β沉积。
Nature. 2023 Jun;618(7964):349-357. doi: 10.1038/s41586-023-06120-6. Epub 2023 May 31.
8
Decreased spliceosome fidelity and egl-8 intron retention inhibit mTORC1 signaling to promote longevity.剪接体保真度降低和 egl-8 内含子保留抑制 mTORC1 信号转导，从而促进长寿。
Nat Aging. 2022 Sep;2(9):796-808. doi: 10.1038/s43587-022-00275-z. Epub 2022 Sep 19.
9
Author Correction: The 4D Nucleome Data Portal as a resource for searching and visualizing curated nucleomics data.作者更正：4D 核体数据门户作为用于搜索和可视化经过整理的核组学数据的资源。
Nat Commun. 2022 Nov 2;13(1):6561. doi: 10.1038/s41467-022-34458-4.
10
X-linked ubiquitin-specific peptidase 11 increases tauopathy vulnerability in women.X 连锁泛素特异性肽酶 11 增加女性 tau 病易感性。
Cell. 2022 Oct 13;185(21):3913-3930.e19. doi: 10.1016/j.cell.2022.09.002. Epub 2022 Oct 4.