Cell reports最新文献_第10页

Spatio-temporal organization of network activity patterns in the hippocampus. 海马体网络活动模式的时空组织。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-06-24 Epub Date: 2025-06-04 DOI: 10.1016/j.celrep.2025.115808

Vítor Lopes-Dos-Santos, Demi Brizee, David Dupret

引用次数: 0

Lysophosphatidic acid and sphingosine-1-phosphate are apical polarity cues in multiple organoid systems. 溶血磷脂酸和鞘氨醇-1-磷酸是多个类器官系统的顶端极性线索。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-06-24 Epub Date: 2025-06-10 DOI: 10.1016/j.celrep.2025.115842

Andrew M Tidball, Jinghui Luo, J Clayton Walker, Charlotte Y Yang, Keithan Lee, Ryan C Spencer, Carissa Matthews, Geshan Feng, Peggy P Hsu, Yusoo Lee, Jack Morgan, Charlie J Childs, Madeline K Eiken, Katherine D Walton, Jason R Spence

{"title":"Lysophosphatidic acid and sphingosine-1-phosphate are apical polarity cues in multiple organoid systems.","authors":"Andrew M Tidball, Jinghui Luo, J Clayton Walker, Charlotte Y Yang, Keithan Lee, Ryan C Spencer, Carissa Matthews, Geshan Feng, Peggy P Hsu, Yusoo Lee, Jack Morgan, Charlie J Childs, Madeline K Eiken, Katherine D Walton, Jason R Spence","doi":"10.1016/j.celrep.2025.115842","DOIUrl":"10.1016/j.celrep.2025.115842","url":null,"abstract":"Apicobasal polarization is crucial for tissue organization during in vivo development and in human organoid models. Extracellular matrix (ECM) signaling typically provides a basal cue, and intestinal and lung organoids reverse polarity from apical-in to apical-out after ECM removal. However, ECM-free brain organoids maintain apical-in polarity, suggesting that media components may influence polarity. Exposing brain organoids to serum induced apical-out orientation. Lysophosphatidic acid (LPA), present in the medium of prior apical-out techniques, was identified as the causative factor. LPA-induced apical-out orientation in brain organoids occurred within 1 day, lasted at least 1 month, and was optimal at human cerebrospinal fluid LPA concentrations. Sphingosine-1-phosphate (S1P) induced similar apical-out polarization. Pharmacological studies revealed that LPA/S1P act via a G-protein coupled receptor/RhoA pathway. Finally, LPA induced apical-out polarity in patient-derived human lung and intestinal organoids, iPSC spheres, and multilineage iPSC-derived intestinal organoids. These findings indicate that LPA signaling is a critical apical polarity cue in multiple tissues.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 6","pages":"115842"},"PeriodicalIF":7.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bright-light treatment ameliorates motor and non-motor deficits through distinct visual circuits in a mouse model of Parkinson's disease. 在帕金森病小鼠模型中，强光治疗通过不同的视觉回路改善了运动和非运动缺陷。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-06-24 Epub Date: 2025-06-13 DOI: 10.1016/j.celrep.2025.115865

Xiaodan Huang, Shengnan Wang, Zhiqing Chen, Wenna Qu, Li Song, Zhengfang Hu, Yue Xi, Yan Yang, Weng-Hei Hong, Song Lin, Kwok-Fai So, Yulong Li, Lu Huang, Qian Tao, Chaoran Ren

{"title":"Bright-light treatment ameliorates motor and non-motor deficits through distinct visual circuits in a mouse model of Parkinson's disease.","authors":"Xiaodan Huang, Shengnan Wang, Zhiqing Chen, Wenna Qu, Li Song, Zhengfang Hu, Yue Xi, Yan Yang, Weng-Hei Hong, Song Lin, Kwok-Fai So, Yulong Li, Lu Huang, Qian Tao, Chaoran Ren","doi":"10.1016/j.celrep.2025.115865","DOIUrl":"10.1016/j.celrep.2025.115865","url":null,"abstract":"Light has a profound impact on non-visual functions, and clinical evidence suggests bright-light therapy's effectiveness in alleviating motor and non-motor symptoms of Parkinson's disease (PD). However, the neural mechanisms underlying these effects remain unclear. Here, we demonstrate that bright-light treatment alleviates PD symptoms in mice via distinct visual circuits. Specifically, bright-light signals transmitted by the ventral lateral geniculate nucleus alleviate non-motor symptoms, such as depressive-like behaviors and spatial memory deficits. Conversely, the improvement in motor symptoms with bright-light treatment depends on a separate, disynaptic visual pathway that connects the superficial layers of the superior colliculus to the substantia nigra pars compacta (SNc). Notably, in this pathway, bright-light signals enhance the bursting activity of SNc dopaminergic neurons by upregulating HCN2 expression, a mechanism essential for motor improvements. These findings provide valuable insights into the neural mechanisms by which bright-light therapy benefits PD.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 6","pages":"115865"},"PeriodicalIF":7.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cohesin supercoils DNA during loop extrusion. 环挤压过程中的内聚蛋白超螺旋DNA。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-06-24 Epub Date: 2025-06-13 DOI: 10.1016/j.celrep.2025.115856

Iain F Davidson, Roman Barth, Kota Nagasaka, Wen Tang, Gordana Wutz, Sabrina Horn, Richard Janissen, Roman R Stocsits, Emilia Chlosta, Benedikt W Bauer, Cees Dekker, Jan-Michael Peters

引用次数: 0

De novo assembly of RNA m⁶A modification factors into viral genome-associated nuclear bodies drives HCMV RNA accumulation. RNA m6A修饰因子在病毒基因组相关核体中的重新组装驱动HCMV RNA积累。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-06-24 DOI: 10.1016/j.celrep.2025.115826

Rebecca C Grande, Chia-Ching Lin, Michael Cammer, Ebube D Emesom, Maaz Asher Khurram, Chris Boutell, Lance T Denes, Timothée Lionnet, Angus C Wilson, Ian Mohr

{"title":"De novo assembly of RNA m6A modification factors into viral genome-associated nuclear bodies drives HCMV RNA accumulation.","authors":"Rebecca C Grande, Chia-Ching Lin, Michael Cammer, Ebube D Emesom, Maaz Asher Khurram, Chris Boutell, Lance T Denes, Timothée Lionnet, Angus C Wilson, Ian Mohr","doi":"10.1016/j.celrep.2025.115826","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115826","url":null,"abstract":"The factors that install and recognize N6-methyladenosine (m6A) on RNA to regulate gene expression are well characterized, but how their spatial organization responds to physiological stress, including infection, is unclear. Here, we show that human cytomegalovirus (HCMV) infection induces accumulation of m6A methyltransferase subunits, including WTAP, together with nuclear m6A reader YTHDC1, into distinctive, membraneless nuclear bodies (NBs) overlapping with incoming virus genomes and immediate-early (IE) RNA transcripts. De novo assembly and integrity of these DNA-associated, IE, virus-activated NBs requires RNAPII transcription, METTL3 m6A methyltransferase activity, and m6A recognition by YTHDC1, but not new protein synthesis. Depleting YTHDC1 or WTAP limits the accumulation of critical HCMV RNAs required for virus DNA replication, interfering with virus reproduction. This reveals a surprising strategy whereby a discrete sub-nuclear RNA biogenesis compartment replete with RNAPII and m6A modification components is swiftly consolidated in proximity to infecting HCMV genomes to initialize and sustain virus gene expression.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 7","pages":"115826"},"PeriodicalIF":7.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reverse engineering neuron-type-specific and type-orthogonal splicing-regulatory networks using diverse cellular transcriptomes. 反向工程神经元类型特异性和类型正交剪接调节网络使用不同的细胞转录组。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-06-24 DOI: 10.1016/j.celrep.2025.115898

Daniel F Moakley, Melissa Campbell, Miquel Anglada-Girotto, Huijuan Feng, Andrea Califano, Edmund Au, Chaolin Zhang

{"title":"Reverse engineering neuron-type-specific and type-orthogonal splicing-regulatory networks using diverse cellular transcriptomes.","authors":"Daniel F Moakley, Melissa Campbell, Miquel Anglada-Girotto, Huijuan Feng, Andrea Califano, Edmund Au, Chaolin Zhang","doi":"10.1016/j.celrep.2025.115898","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115898","url":null,"abstract":"Cell-type-specific alternative splicing (AS) enables differential gene isoform expression between diverse neuron types with distinct identities and functions. Current studies linking individual RNA-binding proteins (RBPs) to AS in a limited number of neuron types underscore the need for holistic modeling. Here, we use network reverse engineering to derive a map of the neuron-type-specific AS-regulatory landscape of 133 mouse neocortical cell types using pseudobulk transcriptomes derived from single-cell data. We infer the regulons of 350 RBPs and their cell-type-specific activities, among which we validate Elavl2 as a key RBP for medial ganglionic eminence (MGE)-specific splicing in GABAergic interneurons using an in vitro embryonic stem cell (ESC) differentiation system. We also identify a module of exons and candidate regulators specific to long- and short-projection neurons across multiple neuronal classes. This study provides a resource for elucidating splicing-regulatory programs that drive neuronal molecular diversity, including those that do not align with gene-expression-based classifications.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 7","pages":"115898"},"PeriodicalIF":7.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ADP-ribosylation of NuMA promotes DNA single-strand break repair and transcription. NuMA的adp核糖基化促进DNA单链断裂修复和转录。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-06-24 Epub Date: 2025-05-20 DOI: 10.1016/j.celrep.2025.115737

Arwa A Abugable, Chunyan Liao, Sarah Antar, Matthew Dowson, Sherif F El-Khamisy

{"title":"ADP-ribosylation of NuMA promotes DNA single-strand break repair and transcription.","authors":"Arwa A Abugable, Chunyan Liao, Sarah Antar, Matthew Dowson, Sherif F El-Khamisy","doi":"10.1016/j.celrep.2025.115737","DOIUrl":"10.1016/j.celrep.2025.115737","url":null,"abstract":"Single-strand breaks (SSBs) are prevalent DNA lesions implicated in genome instability. The nuclear mitotic apparatus protein (NuMA) has been reported to promote SSB repair (SSBR) and regulate transcription following oxidative stress. ADP-ribosylation, an important post-translational modification, regulates several processes, including chromatin remodeling, transcription, and DNA repair. To investigate its role in NuMA-dependent functions, we generated an ADP-ribosylation-deficient NuMA construct and report that NuMA ADP-ribosylation is required for its interaction with tyrosyl DNA phosphodiesterase 1 (TDP1), an SSBR player. Cells expressing ADP-ribosylation-deficient NuMA exhibit delayed SSBR kinetics following oxidative stress and reduced repair at promoter and enhancer regions, consistent with a role of NuMA in protecting non-coding regulatory regions from DNA damage. Furthermore, the expression of NuMA-regulated genes following oxidative stress requires ADP-ribosylation. Our findings demonstrate that ADP-ribosylation of NuMA promotes SSBR and transcription following oxidative stress, underscoring the importance of ADP-ribosylation in modulating DNA repair and gene expression.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 6","pages":"115737"},"PeriodicalIF":7.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Complete reference genome and pangenome improve genome-wide detection and interpretation of DNA methylation using sequencing and array data. 完整的参考基因组和泛基因组利用测序和阵列数据改善了全基因组DNA甲基化的检测和解释。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-06-24 Epub Date: 2025-05-28 DOI: 10.1016/j.celrep.2025.115755

Zheng Dong, Joanne Whitehead, Maggie Fu, Julia L MacIsaac, David H Rehkopf, Luis Rosero-Bixby, Michael S Kobor, Keegan Korthauer

{"title":"Complete reference genome and pangenome improve genome-wide detection and interpretation of DNA methylation using sequencing and array data.","authors":"Zheng Dong, Joanne Whitehead, Maggie Fu, Julia L MacIsaac, David H Rehkopf, Luis Rosero-Bixby, Michael S Kobor, Keegan Korthauer","doi":"10.1016/j.celrep.2025.115755","DOIUrl":"10.1016/j.celrep.2025.115755","url":null,"abstract":"The complete telomere-to-telomere human genome assembly (T2T-CHM13) and the draft human pangenome reference provide unique opportunities to refine DNA methylation (DNAm) studies. Here, we find that T2T-CHM13 calls 7.4% more CpGs genome wide compared to GRCh38 across four widely used short-read DNAm profiling methods and improves the evaluation of probe cross-reactivity and mismatch for Illumina DNAm arrays, yielding new and more reproducible sets of unambiguous probes. The pangenome reference further expands CpG calling by 4.5% in short-read sequencing data and identifies cross-population and population-specific unambiguous probes in DNAm arrays, owing to its improved representation of genetic diversity. These benefits facilitate the discovery of biologically relevant DNAm alterations in epigenome-wide association studies (EWASs). For instance, additional DNAm alterations enriched in cancer-related genes and pathways are identified in cancer EWASs. Together, this study highlights the practical applications of T2T-CHM13 and pangenome for genome biology and provides a basis for expansion of DNAm investigations.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 6","pages":"115755"},"PeriodicalIF":7.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular landscape of sex- and modality-specific exercise adaptation in human skeletal muscle through large-scale multi-omics integration. 通过大规模多组学整合，人类骨骼肌性别和模式特异性运动适应的分子景观。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-06-24 Epub Date: 2025-05-28 DOI: 10.1016/j.celrep.2025.115750

Macsue Jacques, Shanie Landen, Adam P Sharples, Andrew Garnham, Ralf Schittenhelm, Joel Steele, Aino Heikkinen, Elina Sillanpää, Miina Ollikainen, James Broatch, Navabeh Zarekookandeh, Ola Hanson, Ola Ekström, Olof Asplund, Séverine Lamon, Sarah E Alexander, Cassandra Smith, Carlie Bauer, Mary N Woessner, Itamar Levinger, Andrew E Teschendorff, Linn Gillberg, Ida Blom, Jørn Wulff Helge, Nicholas R Harvey, Larisa M Haupt, Lyn R Griffiths, Atul S Deshmukh, Kirsi H Pietiläinen, Päivi Piirilä, Robert A E Seaborne, Marie Klevjer, Anja Bye, Ulrik Wisløff, Bernadette Jones-Freeman, Nir Eynon

{"title":"Molecular landscape of sex- and modality-specific exercise adaptation in human skeletal muscle through large-scale multi-omics integration.","authors":"Macsue Jacques, Shanie Landen, Adam P Sharples, Andrew Garnham, Ralf Schittenhelm, Joel Steele, Aino Heikkinen, Elina Sillanpää, Miina Ollikainen, James Broatch, Navabeh Zarekookandeh, Ola Hanson, Ola Ekström, Olof Asplund, Séverine Lamon, Sarah E Alexander, Cassandra Smith, Carlie Bauer, Mary N Woessner, Itamar Levinger, Andrew E Teschendorff, Linn Gillberg, Ida Blom, Jørn Wulff Helge, Nicholas R Harvey, Larisa M Haupt, Lyn R Griffiths, Atul S Deshmukh, Kirsi H Pietiläinen, Päivi Piirilä, Robert A E Seaborne, Marie Klevjer, Anja Bye, Ulrik Wisløff, Bernadette Jones-Freeman, Nir Eynon","doi":"10.1016/j.celrep.2025.115750","DOIUrl":"10.1016/j.celrep.2025.115750","url":null,"abstract":"We investigated the molecular mechanisms of exercise adaptations in human muscle by integrating genome, methylome, transcriptome, and proteome data from over 1,000 participants (2,340 muscle samples). We identified distinctive signatures associated with maximal oxygen consumption (VO2max), and multi-omics integration uncovered five key genes as robust exercise markers across layers, with transcription factors functioning as activators, synergizing with DNA methylation to regulate gene expression. Minimal sex differences were observed, while modality-specific analysis highlighted distinct pathways for aerobic and resistance exercise, contrasting with muscle disuse patterns. Finally, we created a webtool, OMAx, featuring our individual omics and integration analysis. These findings provide a comprehensive multi-omics framework for understanding exercise-induced molecular adaptations, offering insights into muscle health, cardiorespiratory fitness, and their roles in aging and disease prevention.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 6","pages":"115750"},"PeriodicalIF":7.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

m⁶A RNA methylation-mediated control of global APC expression is required for local translation of β-actin and axon development. m6A RNA甲基化介导的全局APC表达控制是β-肌动蛋白和轴突发育的局部翻译所必需的。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-06-24 Epub Date: 2025-05-20 DOI: 10.1016/j.celrep.2025.115727

Loic Broix, Rohini Roy, Belal Shohayeb, Ikumi Oomoto, Hiroki Umeshima, Dan Ohtan Wang

{"title":"m6A RNA methylation-mediated control of global APC expression is required for local translation of β-actin and axon development.","authors":"Loic Broix, Rohini Roy, Belal Shohayeb, Ikumi Oomoto, Hiroki Umeshima, Dan Ohtan Wang","doi":"10.1016/j.celrep.2025.115727","DOIUrl":"10.1016/j.celrep.2025.115727","url":null,"abstract":"The spatial regulation of mRNAs in neurons, including their localization and translation, is controlled by RNA-binding proteins and is critical for neuronal development. In this study, we present evidence that the multifunctional RNA-binding protein adenomatous polyposis coli (APC) is encoded by an mRNA modified with N6-methyladenosine (m6A). This modification facilitates the translation of APC in neuronal somata via YTH domain-containing family (YTHDF) m6A reader proteins. Disrupted APC expression, caused by reduced expression of the m6A writer METTL14 or reader YTHDF1, or by overexpression of METTL14 mutants carrying human missense mutations linked to autism and schizophrenia, impairs the transport and local translation of APC-regulated target mRNA β-actin in axons and growth cones. Such disruptions consequently hinder axon development both in vitro and in vivo. These findings reveal a mechanism by which m6A-regulated global expression of the RNA-binding protein APC governs axonal mRNA translation and development.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 6","pages":"115727"},"PeriodicalIF":7.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0