Nature Communications最新文献_第3页

Multi-tissue expression and splicing data prioritise anatomical subsite- and sex-specific colorectal cancer susceptibility genes 多组织表达和剪接数据优先考虑解剖亚位点和性别特异性结直肠癌易感基因

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-05-30 DOI: 10.1038/s41467-025-60275-6

Emma Hazelwood, Daffodil M. Canson, Benedita Deslandes, Xuemin Wang, Pik Fang Kho, Danny Legge, Andrei-Emil Constantinescu, Matthew A. Lee, D. Timothy Bishop, Andrew T. Chan, Stephen B. Gruber, Jochen Hampe, Loic Le Marchand, Michael O. Woods, Rish K. Pai, Stephanie L. Schmit, Jane C. Figueiredo, Wei Zheng, Jeroen R. Huyghe, Neil Murphy, Marc J. Gunter, Tom G. Richardson, Vicki L. J. Whitehall, Emma E. Vincent, Dylan M. Glubb, Tracy A. O’Mara

{"title":"Multi-tissue expression and splicing data prioritise anatomical subsite- and sex-specific colorectal cancer susceptibility genes","authors":"Emma Hazelwood, Daffodil M. Canson, Benedita Deslandes, Xuemin Wang, Pik Fang Kho, Danny Legge, Andrei-Emil Constantinescu, Matthew A. Lee, D. Timothy Bishop, Andrew T. Chan, Stephen B. Gruber, Jochen Hampe, Loic Le Marchand, Michael O. Woods, Rish K. Pai, Stephanie L. Schmit, Jane C. Figueiredo, Wei Zheng, Jeroen R. Huyghe, Neil Murphy, Marc J. Gunter, Tom G. Richardson, Vicki L. J. Whitehall, Emma E. Vincent, Dylan M. Glubb, Tracy A. O’Mara","doi":"10.1038/s41467-025-60275-6","DOIUrl":"https://doi.org/10.1038/s41467-025-60275-6","url":null,"abstract":"Genome-wide association studies have suggested numerous colorectal cancer (CRC) susceptibility genes, but their causality and therapeutic potential remain unclear. To prioritise causal associations between gene expression/splicing and CRC risk (52,775 cases; 45,940 controls), we perform a transcriptome-wide association study (TWAS) across six tissues with Mendelian randomisation and colocalisation, integrating sex- and anatomical subsite-specific analyses. Here we reveal 37 genes with robust causal links to CRC risk, ten of which have not previously been reported by TWAS. Most likely causal genes with evidence of cancer cell dependency show elevated expression linked to risk, suggesting therapeutic potential. Notably, SEMA4D, encoding a protein targeted by an investigational CRC therapy, emerges as a key risk gene. We also identify a female-specific association with CRC risk for CCM2 expression and subsite-specific associations, including LAMC1 with rectal cancer risk. These findings offer valuable insights into CRC molecular mechanisms and support promising therapeutic avenues.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"34 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Non-trivial stimuli-responsive collective behaviours emerging from microscopic dynamic complexity in supramolecular polymer systems 超分子聚合物系统中微观动态复杂性中出现的非平凡刺激响应集体行为

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-05-30 DOI: 10.1038/s41467-025-60150-4

Martina Crippa, Claudio Perego, Giovanni M. Pavan

{"title":"Non-trivial stimuli-responsive collective behaviours emerging from microscopic dynamic complexity in supramolecular polymer systems","authors":"Martina Crippa, Claudio Perego, Giovanni M. Pavan","doi":"10.1038/s41467-025-60150-4","DOIUrl":"https://doi.org/10.1038/s41467-025-60150-4","url":null,"abstract":"Supramolecular polymers are composed of monomers that self-assemble non-covalently generating distributions of fibres in continuous exchange-and-communication with each other and the surroundings. Intriguing collective properties may emerge in such molecular-scale complex systems, following mechanisms often difficult to ascertain. Here we show how non-trivial collective behaviours may emerge in dynamical supramolecular polymer systems already at low-complexity levels. We combine minimalistic models, simulations, and advanced statistical analyses investigating how cooperative and non-cooperative supramolecular polymer systems respond to a specific stimulus: i.e., the addition of molecular sequestrators perturbing their equilibrium. Our data show how, while in a non-cooperative system all assemblies populating the system suffer uniformly the perturbation, in a cooperative system the larger/stronger assemblies survive at the expense of the smaller/weaker entities. Collective behaviours typical of larger-scale and more complex (social, economic, etc.) systems may thus emerge even in relatively simple self-assembling systems from the internal (microscopic) dynamic heterogeneity of their ensembles.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"60 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pixel super-resolved virtual staining of label-free tissue using diffusion models 使用扩散模型对无标记组织进行像素超分辨虚拟染色

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-05-30 DOI: 10.1038/s41467-025-60387-z

Yijie Zhang, Luzhe Huang, Nir Pillar, Yuzhu Li, Hanlong Chen, Aydogan Ozcan

{"title":"Pixel super-resolved virtual staining of label-free tissue using diffusion models","authors":"Yijie Zhang, Luzhe Huang, Nir Pillar, Yuzhu Li, Hanlong Chen, Aydogan Ozcan","doi":"10.1038/s41467-025-60387-z","DOIUrl":"https://doi.org/10.1038/s41467-025-60387-z","url":null,"abstract":"Virtual staining of tissue offers a powerful tool for transforming label-free microscopy images of unstained tissue into equivalents of histochemically stained samples. This study presents a diffusion model-based pixel super-resolution virtual staining approach utilizing a Brownian bridge process to enhance both the spatial resolution and fidelity of label-free virtual tissue staining, addressing the limitations of traditional deep learning-based methods. Our approach integrates sampling techniques into a diffusion model-based image inference process to significantly reduce the variance in the generated virtually stained images, resulting in more stable and accurate outputs. Blindly applied to lower-resolution auto-fluorescence images of label-free human lung tissue samples, the diffusion-based pixel super-resolution virtual staining model consistently outperforms conventional approaches in resolution, structural similarity and perceptual accuracy, successfully achieving a pixel super-resolution factor of 4-5×, increasing the output space-bandwidth product by 16-25-fold compared to the input label-free microscopy images. Diffusion-based pixel super-resolved virtual tissue staining not only improves resolution and image quality but also enhances the reliability of virtual staining without traditional chemical staining, offering significant potential for clinical diagnostics.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"146 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bronchopulmonary dysplasia with pulmonary hypertension associates with semaphorin signaling loss and functionally decreased FOXF1 expression 支气管肺发育不良伴肺动脉高压与信号蛋白信号缺失和功能性FOXF1表达降低相关

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-05-30 DOI: 10.1038/s41467-025-60371-7

Shawyon P. Shirazi, Nicholas M. Negretti, Christopher S. Jetter, Alexandria L. Sharkey, Shriya Garg, Meghan E. Kapp, Devan Wilkins, Gabrielle Fortier, Saahithi Mallapragada, Nicholas E. Banovich, Laurie C. Eldredge, Gail H. Deutsch, Christopher V. E. Wright, David B. Frank, Jonathan A. Kropski, Jennifer M. S. Sucre

{"title":"Bronchopulmonary dysplasia with pulmonary hypertension associates with semaphorin signaling loss and functionally decreased FOXF1 expression","authors":"Shawyon P. Shirazi, Nicholas M. Negretti, Christopher S. Jetter, Alexandria L. Sharkey, Shriya Garg, Meghan E. Kapp, Devan Wilkins, Gabrielle Fortier, Saahithi Mallapragada, Nicholas E. Banovich, Laurie C. Eldredge, Gail H. Deutsch, Christopher V. E. Wright, David B. Frank, Jonathan A. Kropski, Jennifer M. S. Sucre","doi":"10.1038/s41467-025-60371-7","DOIUrl":"https://doi.org/10.1038/s41467-025-60371-7","url":null,"abstract":"Lung injury in preterm infants leads to structural and functional respiratory deficits, with a risk for bronchopulmonary dysplasia (BPD) that in its most severe form is accompanied by pulmonary hypertension (PH). To identify potential cellular and molecular drivers of BPD in humans, we performed single-cell RNA sequencing of preterm infant lungs with evolving BPD and BPD + PH compared to term infants. Examination of endothelial cells reveals a unique, aberrant capillary cell-state in BPD + PH defined by ANKRD1 expression. Within the alveolar parenchyma in infants with BPD/BPD + PH, predictive signaling analysis identifies surprising deficits in the semaphorin guidance-cue pathway, with decreased expression of pro-angiogenic transcription factor FOXF1. Loss of semaphorin signaling is replicated in a murine BPD model and in humans with causal FOXF1 mutations for alveolar capillary dysplasia (ACDMPV), suggesting a mechanistic link between developmental programs underlying BPD and ACDMPV and uncovering a critical role for semaphorin signaling in normal lung development.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"57 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Author Correction: An optoelectrochemical synapse based on a single-component n-type mixed conductor 作者更正：基于单组分n型混合导体的光电化学突触

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-05-30 DOI: 10.1038/s41467-025-59570-z

Yazhou Wang, Wentao Shan, Hanrui Li, Yizhou Zhong, Shofarul Wustoni, Johana Uribe, Tianrui Chang, Valentina E. Musteata, Tania Cecilia Hidalgo Castillo, Wan Yue, Haifeng Ling, Nazek El‐Atab, Sahika Inal

引用次数: 0

Degradable film mulching increases soil carbon sequestration in major Chinese dryland agroecosystems 可降解地膜覆盖增加了中国主要旱地农业生态系统的土壤固碳

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-05-30 DOI: 10.1038/s41467-025-60036-5

Zihan Liu, Chenxu Zhao, Nanhai Zhang, Jing Wang, Zhaoyang Li, Yves Uwiragiye, Nyumah Fallah, Thomas W. Crowther, Yuanyuan Huang, Yuanyuan Huang, Yi Xu, Sheng Zhang, Yakov Kuzyakov, Kadambot H. M. Siddique, Zhikuan Jia, Zucong Cai, Scott X. Chang, Minggang Xu, Christoph Müller, Yi Cheng

{"title":"Degradable film mulching increases soil carbon sequestration in major Chinese dryland agroecosystems","authors":"Zihan Liu, Chenxu Zhao, Nanhai Zhang, Jing Wang, Zhaoyang Li, Yves Uwiragiye, Nyumah Fallah, Thomas W. Crowther, Yuanyuan Huang, Yuanyuan Huang, Yi Xu, Sheng Zhang, Yakov Kuzyakov, Kadambot H. M. Siddique, Zhikuan Jia, Zucong Cai, Scott X. Chang, Minggang Xu, Christoph Müller, Yi Cheng","doi":"10.1038/s41467-025-60036-5","DOIUrl":"https://doi.org/10.1038/s41467-025-60036-5","url":null,"abstract":"Plastic film mulching (PM), which contributes to nearly half of the increased crop yields in dryland agroecosystems, exacerbates environmental burdens due to its non-degradable nature. Globally, there is a growing demand to replace non-degradable PM with degradable film mulching (DM), yet its impacts on soil organic carbon (SOC) in dryland agroecosystems remains unknown. Here, using multi-field studies and mesocosm experiments, we found that DM strongly increased but PM reduced SOC storage (0–1 m). This difference is likely attributable to the higher microbial C use efficiency in soil under DM, leading to increased microbial-derived C compared to PM. Under the high roading scenario for 2100, DM could reduce the decomposition of SOC (0–1 m) in China’s drylands by 9.0 ± 1.0 Mg ha–1 year–1 (one standard error) compared with PM. Our findings highlight that DM is a promising alternative to PM for sequestrating SOC and alleviating C loss under climate change in dryland agroecosystems.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"12 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gaseous molecules-mediated electrochemical exfoliation of halogenated MXenes and its boosting in wear-resisting tribovoltaic devices 气体分子介导的卤化MXenes电化学剥离及其在耐磨摩擦伏打器件中的促进作用

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-05-30 DOI: 10.1038/s41467-025-60303-5

Qi Fan, Minghua Chen, Longyi Li, Minghui Li, Chuanxiao Xiao, Tianci Zhao, Long Pan, Ningning Liang, Qing Huang, Lijing Yu, Laipan Zhu, Michael Naguib, Kun Liang

{"title":"Gaseous molecules-mediated electrochemical exfoliation of halogenated MXenes and its boosting in wear-resisting tribovoltaic devices","authors":"Qi Fan, Minghua Chen, Longyi Li, Minghui Li, Chuanxiao Xiao, Tianci Zhao, Long Pan, Ningning Liang, Qing Huang, Lijing Yu, Laipan Zhu, Michael Naguib, Kun Liang","doi":"10.1038/s41467-025-60303-5","DOIUrl":"https://doi.org/10.1038/s41467-025-60303-5","url":null,"abstract":"Two-dimensional transition metal carbides and/or nitrides (MXenes), especially their few-layered nanosheets, have triggered burgeoning research attentions owing to their superiorities including extraordinary electrical conductivity, accessible active surface, and adjustable processability. Molten salts etching route further achieves their controllable surface chemistry. However, the method encounters challenges in achieving few-layered structures due to more complex delamination behaviors. Herein, we present an efficient strategy to fabricate Cl- or Br-terminated MXene nanoflakes with few-layers, achieved by electrochemical intercalation of Li ions and concomitant solvent molecules from the electrolyte solution, with gaseous propylene molecules to disrupt interlayer forces. By controlling cut-off voltages, the optimal protocol results in nanosheets with a recovery rate of ~93% and preserved surface chemistry. The resultant MXenes dispersions were employed as lubricants to enhance tribovoltaic nanogenerators, where Ti3C2Br2 displayed superior electrical output. These findings facilitate the understanding of MXenes’ intrinsic physical properties and enable the nanoengineering of advanced electronic devices.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"19 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cleavage of CAD by caspase-3 determines the cancer cell fate during chemotherapy caspase-3对CAD的切割决定了化疗期间癌细胞的命运

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-05-30 DOI: 10.1038/s41467-025-60144-2

Jingsong Ma, Jiabao Zhao, Chensong Zhang, Jinshui Tan, Ao Cheng, Zhuo Niu, Zeyang Lin, Guangchao Pan, Chao Chen, Yang Ding, Mengya Zhong, Yifan Zhuang, Yubo Xiong, Huiwen Zhou, Shengyi Zhou, Meijuan Xu, Wenjie Ye, Funan Li, Yongxi Song, Zhenning Wang, Xuehui Hong

{"title":"Cleavage of CAD by caspase-3 determines the cancer cell fate during chemotherapy","authors":"Jingsong Ma, Jiabao Zhao, Chensong Zhang, Jinshui Tan, Ao Cheng, Zhuo Niu, Zeyang Lin, Guangchao Pan, Chao Chen, Yang Ding, Mengya Zhong, Yifan Zhuang, Yubo Xiong, Huiwen Zhou, Shengyi Zhou, Meijuan Xu, Wenjie Ye, Funan Li, Yongxi Song, Zhenning Wang, Xuehui Hong","doi":"10.1038/s41467-025-60144-2","DOIUrl":"https://doi.org/10.1038/s41467-025-60144-2","url":null,"abstract":"Metabolic heterogeneity resulting from the intra-tumoral heterogeneity mediates massive adverse outcomes of tumor therapy, including chemotherapeutic resistance, but the mechanisms inside remain largely unknown. Here, we find that the de novo pyrimidine synthesis pathway determines the chemosensitivity. Chemotherapeutic drugs promote the degradation of cytosolic Carbamoyl-phosphate synthetase II, Aspartate transcarbamylase, and Dihydroorotase (CAD), an enzyme that is rate-limiting for pyrimidine synthesis, leading to apoptosis. We also find that CAD needs to be cleaved by caspase-3 on its Asp1371 residue, before its degradation. Overexpressing CAD or mutating Asp1371 to block caspase-3 cleavage confers chemoresistance in xenograft and Cldn18-ATK gastric cancer models. Importantly, mutations related to Asp1371 of CAD are found in tumor samples that failed neoadjuvant chemotherapy and pharmacological targeting of CAD-Asp1371 mutations using RMY-186 ameliorates chemotherapy efficacy. Our work reveals the vulnerability of de novo pyrimidine synthesis during chemotherapy, highlighting CAD as a promising therapeutic target and biomarker.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"26 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Spatially regulated water-heat transport by fluidic diode membrane for efficient solar-powered desalination and electricity generation 利用流体二极管膜进行空间调节的水热传输，用于高效的太阳能脱盐和发电

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-05-30 DOI: 10.1038/s41467-025-60283-6

Yuanhang Cao, Jiemin Wang, Weixin Guan, Meng An, Peng Yan, Zhengtong Li, Changsheng Zhao, Guihua Yu

{"title":"Spatially regulated water-heat transport by fluidic diode membrane for efficient solar-powered desalination and electricity generation","authors":"Yuanhang Cao, Jiemin Wang, Weixin Guan, Meng An, Peng Yan, Zhengtong Li, Changsheng Zhao, Guihua Yu","doi":"10.1038/s41467-025-60283-6","DOIUrl":"https://doi.org/10.1038/s41467-025-60283-6","url":null,"abstract":"Interfacial solar-driven evaporation has attracted great research interests, given its high conversion efficiency of solar energy and transformative industrial potential for desalination. However, current evaporators with porous volume remain critical challenges by inherently balancing efficient fluid transport and effective heat localization. Herein, we propose the strategy and design of lightweight, flexible and monolayered fluidic diode membrane-based evaporators, featuring regularly arrayed macropores and dense nanopores on each side. Such a delicate microstructure offers universality in establishing asymmetric channels along macroporous-to-nanoporous to enable the diode-like directional water transport as well as facilitate the heat localization on the nanopores side. Consequently, a high evaporation rate of a maximum 3.82 kg m−2 h−1 can be achieved under 1 sun illumination, exceeding most 2D and 3D evaporators. Besides, the durability and practicability of our evaporators are validated through salt resistance tests, purification experiments among various contaminants, and outdoor evaluations. Moreover, the structure engineering and water-transport optimization of fluidic diode membranes also offer potentials for hydrovoltaic applications, with over 1.6 V generated by tandem devices at the ambient environment. This work provides a concept for designing high-performance monolayered membranes applicable in environmental and energy-related realms.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"1 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CRISPR screen decodes SWI/SNF chromatin remodeling complex assembly CRISPR筛选解码SWI/SNF染色质重塑复合体组装

IF 16.6 1区综合性期刊

Nature Communications Pub Date : 2025-05-30 DOI: 10.1038/s41467-025-60424-x

Hanna Schwaemmle, Hadrien Soldati, Nikolaos M. R. Lykoskoufis, Mylène Docquier, Alexandre Hainard, Simon M. G. Braun

{"title":"CRISPR screen decodes SWI/SNF chromatin remodeling complex assembly","authors":"Hanna Schwaemmle, Hadrien Soldati, Nikolaos M. R. Lykoskoufis, Mylène Docquier, Alexandre Hainard, Simon M. G. Braun","doi":"10.1038/s41467-025-60424-x","DOIUrl":"https://doi.org/10.1038/s41467-025-60424-x","url":null,"abstract":"The SWI/SNF (or BAF) complex is an essential chromatin remodeler, which is frequently mutated in cancer and neurodevelopmental disorders. These are often heterozygous loss-of-function mutations, indicating a dosage-sensitive role for SWI/SNF subunits. However, the molecular mechanisms regulating SWI/SNF subunit dosage to ensure complex assembly remain largely unexplored. We performed a CRISPR KO screen, using epigenome editing in mouse embryonic stem cells, and identified Mlf2 and Rbm15 as regulators of SWI/SNF complex activity. First, we show that MLF2, a poorly characterized chaperone protein, promotes SWI/SNF assembly and binding to chromatin. Rapid degradation of MLF2 reduces chromatin accessibility at sites that depend on high levels of SWI/SNF binding to maintain open chromatin. Next, we find that RBM15, part of the m6A writer complex, controls m6A modifications on specific SWI/SNF mRNAs to regulate subunit protein levels. Misregulation of m6A methylation causes overexpression of core SWI/SNF subunits leading to the assembly of incomplete complexes lacking the catalytic ATPase/ARP subunits. These data indicate that targeting modulators of SWI/SNF complex assembly may offer a potent therapeutic strategy for diseases associated with impaired chromatin remodeling.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"25 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0