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Dynamically organized chromatin complexes often involve multiplex chromatin interactions and sometimes chromatin-associated RNA 1-3 . Chromatin complex compositions change during cellular differentiation and ageing, and are expected to be highly heterogeneous among terminally differentiated single cells 4-7 . 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 between cis expression quantitative trait loci and a promoter tends to be that in which these cis expression 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.

Titel:	Single-cell multiplex chromatin and RNA interactions in ageing human brain.
Autor/in / Beteiligte Person:	Wen, X ; Luo, Z ; Zhao, W ; Calandrelli, R ; Nguyen, TC ; Wan, X ; Charles Richard, JL ; Zhong, S
Zeitschrift:	Nature, Jg. 628 (2024-04-01), Heft 8008, S. 648-656
Veröffentlichung:	Basingstoke : Nature Publishing Group ; <i>Original Publication</i>: London, Macmillan Journals ltd., 2024
Medientyp:	academicJournal
ISSN:	1476-4687 (electronic)
DOI:	10.1038/s41586-024-07239-w
Schlagwort:	Aged Female Humans Male Alzheimer Disease genetics Alzheimer Disease pathology Cellular Senescence genetics Chromosomes, Human, X genetics Chromosomes, Human, X metabolism Gene Expression Profiling methods Promoter Regions, Genetic Quantitative Trait Loci RNA, Long Noncoding genetics RNA, Long Noncoding metabolism Transcription, Genetic Aging genetics Cell Nucleus genetics Chromatin genetics Chromatin metabolism Frontal Lobe metabolism RNA genetics RNA metabolism Single-Cell Analysis methods
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Nature] 2024 Apr; Vol. 628 (8008), pp. 648-656. <i>Date of Electronic Publication: </i>2024 Mar 27. MeSH Terms: Aging* / genetics ; Cell Nucleus* / genetics ; Chromatin* / genetics ; Chromatin* / metabolism ; Frontal Lobe* / metabolism ; RNA* / genetics ; RNA* / metabolism ; Single-Cell Analysis* / methods ; Aged ; Female ; Humans ; Male ; Alzheimer Disease / genetics ; Alzheimer Disease / pathology ; Cellular Senescence / genetics ; Chromosomes, Human, X / genetics ; Chromosomes, Human, X / metabolism ; Gene Expression Profiling / methods ; Promoter Regions, Genetic ; Quantitative Trait Loci ; RNA, Long Noncoding / genetics ; RNA, Long Noncoding / metabolism ; Transcription, Genetic Comments: Update of: bioRxiv. 2024 Mar 04;:. (PMID: 37425846) References: Quinodoz, S. A. et al. RNA promotes the formation of spatial compartments in the nucleus. Cell 184, 5775–5790 (2021). (PMID: 34739832911587710.1016/j.cell.2021.10.014) ; Calandrelli, R. et al. Genome-wide analysis of the interplay between chromatin-associated RNA and 3D genome organization in human cells. Nat. Commun. 14, 6519 (2023). (PMID: 378452341057926410.1038/s41467-023-42274-7) ; Li, X. & Fu, X.-D. Chromatin-associated RNAs as facilitators of functional genomic interactions. Nat. Rev. Genet. 20, 503–519 (2019). (PMID: 31160792768497910.1038/s41576-019-0135-1) ; Nagano, T. et al. Cell-cycle dynamics of chromosomal organization at single-cell resolution. Nature 547, 61–67 (2017). (PMID: 28682332556781210.1038/nature23001) ; Flyamer, I. M. et al. Single-nucleus Hi-C reveals unique chromatin reorganization at oocyte-to-zygote transition. Nature 544, 110–114 (2017). (PMID: 28355183563969810.1038/nature21711) ; Ramani, V. et al. Massively multiplex single-cell Hi-C. Nat. Methods 14, 263–266 (2017). (PMID: 28135255533080910.1038/nmeth.4155) ; Stevens, T. J. et al. 3D structures of individual mammalian genomes studied by single-cell Hi-C. Nature 544, 59–64 (2017). (PMID: 28289288538513410.1038/nature21429) ; Lupiáñez, D. G. et al. Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions. Cell 161, 1012–1025 (2015). (PMID: 25959774479153810.1016/j.cell.2015.04.004) ; Dekker, J. et al. The 4D nucleome project. Nature 549, 219–226 (2017). (PMID: 28905911561733510.1038/nature23884) ; Sun, J. H. et al. Disease-associated short tandem repeats co-localize with chromatin domain boundaries. Cell 175, 224–238 (2018). (PMID: 30173918617560710.1016/j.cell.2018.08.005) ; Rao, S. S. P. et al. Cohesin loss eliminates all loop domains. Cell 171, 305–320 (2017). (PMID: 28985562584648210.1016/j.cell.2017.09.026) ; Arrastia, M. V. et al. Single-cell measurement of higher-order 3D genome organization with scSPRITE. Nat. Biotechnol. 40, 64–73 (2022). (PMID: 3442670310.1038/s41587-021-00998-1) ; Takei, Y. et al. Integrated spatial genomics reveals global architecture of single nuclei. Nature 590, 344–350 (2021). (PMID: 33505024787843310.1038/s41586-020-03126-2) ; Chen, K. H., Boettiger, A. N., Moffitt, J. R., Wang, S. & Zhuang, X. Spatially resolved, highly multiplexed RNA profiling in single cells. Science 348, aaa6090 (2015). (PMID: 25858977466268110.1126/science.aaa6090) ; Zhu, C., Preissl, S. & Ren, B. Single-cell multimodal omics: the power of many. Nat. Methods 17, 11–14 (2020). (PMID: 3190746210.1038/s41592-019-0691-5) ; Chen, S., Lake, B. B. & Zhang, K. High-throughput sequencing of the transcriptome and chromatin accessibility in the same cell. Nat. Biotechnol. 37, 1452–1457 (2019). (PMID: 31611697689313810.1038/s41587-019-0290-0) ; Plongthongkum, N., Diep, D., Chen, S., Lake, B. B. & Zhang, K. Scalable dual-omics profiling with single-nucleus chromatin accessibility and mRNA expression sequencing 2 (SNARE-seq2). Nat. Protoc. 16, 4992–5029 (2021). (PMID: 3465027810.1038/s41596-021-00507-3) ; Ma, S. et al. Chromatin potential identified by shared single-cell profiling of RNA and chromatin. Cell 183, 1103–1116 (2020). (PMID: 33098772766973510.1016/j.cell.2020.09.056) ; Liu, Z. et al. Linking genome structures to functions by simultaneous single-cell Hi-C and RNA-seq. Science 380, 1070–1076 (2023). (PMID: 3728987510.1126/science.adg3797) ; Zheng, M. et al. Multiplex chromatin interactions with single-molecule precision. Nature 566, 558–562 (2019). (PMID: 30778195700187510.1038/s41586-019-0949-1) ; Deshpande, A. S. et al. Identifying synergistic high-order 3D chromatin conformations from genome-scale nanopore concatemer sequencing. Nat. Biotechnol. 40, 1488–1499 (2022). (PMID: 3563742010.1038/s41587-022-01289-z) ; Quinodoz, S. A. et al. Higher-order inter-chromosomal hubs shape 3D genome organization in the nucleus. Cell 174, 744–757 (2018). (PMID: 29887377654832010.1016/j.cell.2018.05.024) ; Thakur, J. & Henikoff, S. Architectural RNA in chromatin organization. Biochem. Soc. Trans. 48, 1967–1978 (2020). (PMID: 32897323760902610.1042/BST20191226) ; Rinn, J. L. & Chang, H. Y. Genome regulation by long noncoding RNAs. Annu. Rev. Biochem. 81, 145–166 (2012). (PMID: 2266307810.1146/annurev-biochem-051410-092902) ; Lee, J. T. Gracefully ageing at 50, X-chromosome inactivation becomes a paradigm for RNA and chromatin control. Nat. Rev. Mol. Cell Biol. 12, 815–826 (2011). (PMID: 2210860010.1038/nrm3231) ; Tukiainen, T. et al. Landscape of X chromosome inactivation across human tissues. Nature 550, 244–248 (2017). (PMID: 29022598568519210.1038/nature24265) ; Yan, Y. et al. X-linked ubiquitin-specific peptidase 11 increases tauopathy vulnerability in women. Cell 185, 3913–3930 (2022). (PMID: 36198316958869710.1016/j.cell.2022.09.002) ; Yan, Z. et al. Genome-wide colocalization of RNA–DNA interactions and fusion RNA pairs. Proc. Natl Acad. Sci. USA 116, 3328–3337 (2019). (PMID: 30718424638672310.1073/pnas.1819788116) ; Wu, W. et al. Mapping RNA–chromatin interactions by sequencing with iMARGI. Nat. Protoc. 14, 3243–3272 (2019). (PMID: 31619811731452810.1038/s41596-019-0229-4) ; Li, X. et al. GRID-seq reveals the global RNA–chromatin interactome. Nat. Biotechnol. 35, 940–950 (2017). (PMID: 28922346595355510.1038/nbt.3968) ; Bell, J. C. et al. Chromatin-associated RNA sequencing (ChAR-seq) maps genome-wide RNA-to-DNA contacts. eLife 7, e27024 (2018). (PMID: 29648534596234010.7554/eLife.27024) ; Bonetti, A. et al. RADICL-seq identifies general and cell type-specific principles of genome-wide RNA-chromatin interactions. Nat. Commun. 11, 1018 (2020). (PMID: 32094342703987910.1038/s41467-020-14337-6) ; Lieberman-Aiden, E. et al. Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326, 289–293 (2009). (PMID: 19815776285859410.1126/science.1181369) ; Krietenstein, N. et al. Ultrastructural details of mammalian chromosome architecture. Mol. Cell 78, 554–565 (2020). (PMID: 32213324722262510.1016/j.molcel.2020.03.003) ; Encode Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature 489, 57–74 (2012). ; Beach, T. G. et al. Arizona study of aging and neurodegenerative disorders and brain and body donation program. Neuropathology 35, 354–389 (2015). ; Deming, Y. et al. The MS4A gene cluster is a key modulator of soluble TREM2 and Alzheimer’s disease risk. Sci. Transl. Med. 11, eaau2291 (2019). (PMID: 31413141669705310.1126/scitranslmed.aau2291) ; Mathys, H. et al. Single-cell transcriptomic analysis of Alzheimer’s disease. Nature 570, 332–337 (2019). (PMID: 31042697686582210.1038/s41586-019-1195-2) ; Cerghet, M. et al. Proliferation and death of oligodendrocytes and myelin proteins are differentially regulated in male and female rodents. J. Neurosci. 26, 1439–1447 (2006). (PMID: 16452667667548110.1523/JNEUROSCI.2219-05.2006) ; Tan, L. et al. Lifelong restructuring of 3D genome architecture in cerebellar granule cells. Science 381, 1112–1119 (2023). (PMID: 376769451105918910.1126/science.adh3253) ; Bhadra, M., Howell, P., Dutta, S., Heintz, C. & Mair, W. B. Alternative splicing in aging and longevity. Hum. Genet. 139, 357–369 (2020). (PMID: 3183449310.1007/s00439-019-02094-6) ; Huang, W. et al. Decreased spliceosome fidelity and egl-8 intron retention inhibit mTORC1 signaling to promote longevity. Nat. Aging 2, 796–808 (2022). (PMID: 371185031015423610.1038/s43587-022-00275-z) ; Mao, S. et al. A transcriptome-based single-cell biological age model and resource for tissue-specific aging measures. Genome Res. 33, 1381–1394 (2023). (PMID: 375244361054725210.1101/gr.277491.122) ; Xiong, X. et al. Epigenomic dissection of Alzheimer’s disease pinpoints causal variants and reveals epigenome erosion. Cell 186, 4422–4437 (2023). (PMID: 3777468010.1016/j.cell.2023.08.040) ; Bryois, J. et al. Cell-type-specific cis-eQTLs in eight human brain cell types identify novel risk genes for psychiatric and neurological disorders. Nat. Neurosci. 25, 1104–1112 (2022). (PMID: 3591517710.1038/s41593-022-01128-z) ; Weakley, S. M., Wang, H., Yao, Q. & Chen, C. Expression and function of a large non-coding RNA gene XIST in human cancer. World J. Surg. 35, 1751–1756 (2011). (PMID: 21212949327508310.1007/s00268-010-0951-0) ; Disteche, C. M. Dosage compensation of the sex chromosomes. Annu. Rev. Genet. 46, 537–560 (2012). (PMID: 22974302376730710.1146/annurev-genet-110711-155454) ; Lee, J. T. Epigenetic regulation by long noncoding RNAs. Science 338, 1435–1439 (2012). (PMID: 2323972810.1126/science.1231776) ; Takei, Y. et al. Single-cell nuclear architecture across cell types in the mouse brain. Science 374, 586–594 (2021). (PMID: 3459159210.1126/science.abj1966) ; Yu, R., McCauley, B. & Dang, W. Loss of chromatin structural integrity is a source of stress during aging. Hum. Genet. 139, 371–380 (2020). (PMID: 31900586801143210.1007/s00439-019-02100-x) ; Mazuir, E., Fricker, D. & Sol-Foulon, N. Neuron-oligodendrocyte communication in myelination of cortical GABAergic cells. Life (Basel) 11, 216 (2021). ; Depp, C. et al. Myelin dysfunction drives amyloid-β deposition in models of Alzheimer’s disease. Nature 618, 349–357 (2023). (PMID: 372586781024738010.1038/s41586-023-06120-6) ; Holmes, D. S., Mayfield, J. E., Sander, G. & Bonner, J. Chromosomal RNA: its properties. Science 177, 72–74 (1972). (PMID: 504177910.1126/science.177.4043.72) ; Rodríguez-Campos, A. & Azorín, F. RNA is an integral component of chromatin that contributes to its structural organization. PLoS ONE 2, e1182 (2007). (PMID: 18000552206351610.1371/journal.pone.0001182) ; Nguyen, D. K. & Disteche, C. M. Dosage compensation of the active X chromosome in mammals. Nat. Genet. 38, 47–53 (2006). (PMID: 1634122110.1038/ng1705) ; Hawkins, J. A., Jones, S. K. Jr, Finkelstein, I. J. & Press, W. H. Indel-correcting DNA barcodes for high-throughput sequencing. Proc. Natl Acad. Sci. USA 115, E6217–E6226 (2018). ; Köster, J. & Rahmann, S. Snakemake—a scalable bioinformatics workflow engine. Bioinformatics 28, 2520–2522 (2012). (PMID: 2290821510.1093/bioinformatics/bts480) ; Martin, M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet J. 17, 10–12 (2011). (PMID: 10.14806/ej.17.1.200) ; Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–359 (2012). (PMID: 22388286332238110.1038/nmeth.1923) ; Korsunsky, I. et al. Fast, sensitive and accurate integration of single-cell data with Harmony. Nat. Methods 16, 1289–1296 (2019). (PMID: 31740819688469310.1038/s41592-019-0619-0) ; Reiff, S. B. et al. Author correction: the 4D Nucleome data portal as a resource for searching and visualizing curated nucleomics data. Nat. Commun. 13, 6561 (2022). (PMID: 36323678963038110.1038/s41467-022-34458-4) ; Durand, N. C. et al. Juicebox provides a visualization system for Hi-C contact maps with unlimited zoom. Cell Syst. 3, 99–101 (2016). (PMID: 27467250559692010.1016/j.cels.2015.07.012) ; Open2C et al. Cooltools: enabling high-resolution Hi-C analysis in Python. Preprint at bioRxiv https://doi.org/10.1101/2022.10.31.514564 (2022). ; Frankish, A. et al. GENCODE 2021. Nucleic Acids Res. 49, D916–D923 (2021). (PMID: 3327011110.1093/nar/gkaa1087) ; Hao, Y. et al. Integrated analysis of multimodal single-cell data. Cell 184, 3573–3587 (2021). (PMID: 34062119823849910.1016/j.cell.2021.04.048) ; Stuart, T. et al. Comprehensive integration of single-cell data. Cell 177, 1888–1902 (2019). (PMID: 31178118668739810.1016/j.cell.2019.05.031) ; Bakken, T. E. et al. Comparative cellular analysis of motor cortex in human, marmoset and mouse. Nature 598, 111–119 (2021). (PMID: 34616062849464010.1038/s41586-021-03465-8) ; Franzén, O., Gan, L.-M. & Björkegren, J. L. M. PanglaoDB: a web server for exploration of mouse and human single-cell RNA sequencing data. Database (Oxford) 2019, baz046 (2019). ; Kolberg, L., Raudvere, U., Kuzmin, I., Vilo, J. & Peterson, H. gprofiler2 - An R package for gene list functional enrichment analysis and namespace conversion toolset g:Profiler. F1000Res. 9, ELIXIR-709 (2020). (PMID: 33564394785984110.12688/f1000research.24956.2) ; Wen, X. MUSIC-docker. GitHub https://github.com/Zhong-Lab-UCSD/MUSIC-docker (2024). ; Wen, X. MUSIC-tools. GitHub https://github.com/Zhong-Lab-UCSD/MUSIC-tools (2024). Grant Information: U01 CA200147 United States CA NCI NIH HHS; R01 HD107206 United States HD NICHD NIH HHS; P30 AG072980 United States AG NIA NIH HHS; R01 GM138852 United States GM NIGMS NIH HHS; DP1 DK126138 United States DK NIDDK NIH HHS; UH3 CA256960 United States CA NCI NIH HHS; U24 NS072026 United States NS NINDS NIH HHS; P30 AG019610 United States AG NIA NIH HHS Substance Nomenclature: 0 (Chromatin) ; 63231-63-0 (RNA) ; 0 (RNA, Long Noncoding) ; 0 (XIST non-coding RNA) Entry Date(s): Date Created: 20240328 Date Completed: 20240419 Latest Revision: 20240524 Update Code: 20240525 PubMed Central ID: PMC11023937

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