Cell reports最新文献

Diribonuclease activity eliminates toxic diribonucleotide accumulation 地里核酸酶活性可消除有毒地里核苷酸的积累

IF 8.8 1区生物学

Cell reports Pub Date : 2024-09-13 DOI: 10.1016/j.celrep.2024.114759

引用次数: 0

Integrative identification of non-coding regulatory regions driving metastatic prostate cancer 整合鉴定驱动转移性前列腺癌的非编码调控区

IF 8.8 1区生物学

Cell reports Pub Date : 2024-09-13 DOI: 10.1016/j.celrep.2024.114764

Brian J. Woo, Ruhollah Moussavi-Baygi, Heather Karner, Mehran Karimzadeh, Hassan Yousefi, Sean Lee, Kristle Garcia, Tanvi Joshi, Keyi Yin, Albertas Navickas, Luke A. Gilbert, Bo Wang, Hosseinali Asgharian, Felix Y. Feng, Hani Goodarzi

{"title":"Integrative identification of non-coding regulatory regions driving metastatic prostate cancer","authors":"Brian J. Woo, Ruhollah Moussavi-Baygi, Heather Karner, Mehran Karimzadeh, Hassan Yousefi, Sean Lee, Kristle Garcia, Tanvi Joshi, Keyi Yin, Albertas Navickas, Luke A. Gilbert, Bo Wang, Hosseinali Asgharian, Felix Y. Feng, Hani Goodarzi","doi":"10.1016/j.celrep.2024.114764","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114764","url":null,"abstract":"Large-scale sequencing efforts have been undertaken to understand the mutational landscape of the coding genome. However, the vast majority of variants occur within non-coding genomic regions. We designed an integrative computational and experimental framework to identify recurrently mutated non-coding regulatory regions that drive tumor progression. Applying this framework to sequencing data from a large prostate cancer patient cohort revealed a large set of candidate drivers. We used (1) in silico analyses, (2) massively parallel reporter assays, and (3) in vivo CRISPR interference screens to systematically validate metastatic castration-resistant prostate cancer (mCRPC) drivers. One identified enhancer region, GH22I030351, acts on a bidirectional promoter to simultaneously modulate expression of the U2-associated splicing factor SF3A1 and chromosomal protein CCDC157. SF3A1 and CCDC157 promote tumor growth in vivo. We nominated a number of transcription factors, notably SOX6, to regulate expression of SF3A1 and CCDC157. Our integrative approach enables the systematic detection of non-coding regulatory regions that drive human cancers.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222206","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

Dynamic phosphorylation of FOXA1 by Aurora B guides post-mitotic gene reactivation 极光 B 对 FOXA1 的动态磷酸化引导着有丝分裂后的基因再激活

IF 8.8 1区生物学

Cell reports Pub Date : 2024-09-13 DOI: 10.1016/j.celrep.2024.114739

Ting Zhang, Shuaiyu Liu, Olanrewaju Durojaye, Fangyuan Xiong, Zhiyou Fang, Tahir Ullah, Chuanhai Fu, Bo Sun, Hao Jiang, Peng Xia, Zhikai Wang, Xuebiao Yao, Xing Liu

{"title":"Dynamic phosphorylation of FOXA1 by Aurora B guides post-mitotic gene reactivation","authors":"Ting Zhang, Shuaiyu Liu, Olanrewaju Durojaye, Fangyuan Xiong, Zhiyou Fang, Tahir Ullah, Chuanhai Fu, Bo Sun, Hao Jiang, Peng Xia, Zhikai Wang, Xuebiao Yao, Xing Liu","doi":"10.1016/j.celrep.2024.114739","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114739","url":null,"abstract":"FOXA1 serves as a crucial pioneer transcription factor during developmental processes and plays a pivotal role as a mitotic bookmarking factor to perpetuate gene expression profiles and maintain cellular identity. During mitosis, the majority of FOXA1 dissociates from specific DNA binding sites and redistributes to non-specific binding sites; however, the regulatory mechanisms governing molecular dynamics and activity of FOXA1 remain elusive. Here, we show that mitotic kinase Aurora B specifies the different DNA binding modes of FOXA1 and guides FOXA1 biomolecular condensation in mitosis. Mechanistically, Aurora B kinase phosphorylates FOXA1 at Serine 221 (S221) to liberate the specific, but not the non-specific, DNA binding. Interestingly, the phosphorylation of S221 attenuates the FOXA1 condensation that requires specific DNA binding. Importantly, perturbation of the dynamic phosphorylation impairs accurate gene reactivation and cell proliferation, suggesting that reversible mitotic protein phosphorylation emerges as a fundamental mechanism for the spatiotemporal control of mitotic bookmarking.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222208","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

Cross-regulations of two connected domains form a mechanical circuit for steady force transmission during clathrin-mediated endocytosis 在凝集素介导的内吞过程中，两个相连结构域的交叉调节形成了稳定传力的机械回路

IF 8.8 1区生物学

Cell reports Pub Date : 2024-09-13 DOI: 10.1016/j.celrep.2024.114725

Yuan Ren, Jie Yang, Barbara Fujita, Yongli Zhang, Julien Berro

{"title":"Cross-regulations of two connected domains form a mechanical circuit for steady force transmission during clathrin-mediated endocytosis","authors":"Yuan Ren, Jie Yang, Barbara Fujita, Yongli Zhang, Julien Berro","doi":"10.1016/j.celrep.2024.114725","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114725","url":null,"abstract":"Mechanical forces are transmitted from the actin cytoskeleton to the membrane during clathrin-mediated endocytosis (CME) in the fission yeast Schizosaccharomyces pombe. End4p directly transmits force in CME by binding to both the membrane (through the AP180 N-terminal homology [ANTH] domain) and F-actin (through the talin-HIP1/R/Sla2p actin-tethering C-terminal homology [THATCH] domain). We show that 7 pN force is required for stable binding between THATCH and F-actin. We also characterized a domain in End4p, Rend (rod domain in End4p), that resembles R12 of talin. Membrane localization of Rend primes the binding of THATCH to F-actin, and force-induced unfolding of Rend at 15 pN terminates the transmission of force. We show that the mechanical properties (mechanical stability, unfolding extension, hysteresis) of Rend and THATCH are tuned to form a circuit for the initiation, transmission, and termination of force between the actin cytoskeleton and membrane. The mechanical circuit by Rend and THATCH may be conserved and coopted evolutionarily in cell adhesion complexes.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222207","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

Dynamic ensemble balance in direct- and indirect-pathway striatal projection neurons underlying decision-related action selection 直接和间接通路纹状体投射神经元的动态集合平衡是决策相关行动选择的基础

IF 8.8 1区生物学

Cell reports Pub Date : 2024-09-13 DOI: 10.1016/j.celrep.2024.114726

Shunhang Tang, Lele Cui, Jingwei Pan, Ning-long Xu

{"title":"Dynamic ensemble balance in direct- and indirect-pathway striatal projection neurons underlying decision-related action selection","authors":"Shunhang Tang, Lele Cui, Jingwei Pan, Ning-long Xu","doi":"10.1016/j.celrep.2024.114726","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114726","url":null,"abstract":"The posterior dorsal striatum (pDS) plays an essential role in sensory-guided decision-making. However, it remains unclear how the antagonizing direct- and indirect-pathway striatal projection neurons (dSPNs and iSPNs) work in concert to support action selection. Here, we employed deep-brain two-photon imaging to investigate pathway-specific single-neuron and population representations during an auditory-guided decision-making task. We found that the majority of pDS projection neurons predominantly encode choice information. Both dSPNs and iSPNs comprise divergent subpopulations of comparable sizes representing competing choices, rendering a multi-ensemble balance between the two pathways. Intriguingly, such ensemble balance displays a dynamic shift during the decision period: dSPNs show a significantly stronger preference for the contraversive choice than iSPNs. This dynamic shift is further manifested in the inter-neuronal coactivity and population trajectory divergence. Our results support a balance-shift model as a neuronal population mechanism coordinating the direct and indirect striatal pathways for eliciting selected actions during decision-making.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222211","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

Multi-trait analysis reveals risk loci for heart failure and the shared genetic etiology with blood lipids, blood pressure, and blood glucose 多性状分析揭示了心力衰竭的风险基因位点以及与血脂、血压和血糖的共同遗传病因

IF 8.8 1区生物学

Cell reports Pub Date : 2024-09-13 DOI: 10.1016/j.celrep.2024.114735

Yanchen Zhu, Yahui Wang, Zhaorui Cui, Fani Liu, Chunyu Hu, Jiqiang Hu

{"title":"Multi-trait analysis reveals risk loci for heart failure and the shared genetic etiology with blood lipids, blood pressure, and blood glucose","authors":"Yanchen Zhu, Yahui Wang, Zhaorui Cui, Fani Liu, Chunyu Hu, Jiqiang Hu","doi":"10.1016/j.celrep.2024.114735","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114735","url":null,"abstract":"Phenotypic associations have been reported between heart failure (HF) and blood lipids (BLs), blood pressure (BP), and blood glucose (BG). However, the shared genetic etiology underlying these associations remains incompletely understood. Conducting a large-scale multi-trait association study for HF with these traits, we discovered 143 previously unreported genomic risk loci for HF. Results showed that 46, 35, and 14 colocalized loci were shared by HF with BLs, BP, and BG, respectively. Notably, the loci shared by HF with these traits rarely overlapped, indicating distinct mechanisms. The combination of gene-mapping, gene-based, and transcriptome-wide association analyses prioritized noteworthy candidate genes (such as lipoprotein lipase [LPL], G protein-coupled receptor kinase 5 [GRK5], and troponin C1, slow skeletal and cardiac type [TNNC1]) for HF. Enrichment analysis revealed that HF exhibited comparable characteristics to cardiovascular traits and metabolic traits correlated to BLs, BP, and BG. Finally, we reported drug repurposing candidates and plasma protein targets for HF. These results provide biological insights into the pathogenesis of these comorbidities of HF.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222209","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

Inferotemporal face patches are histo-architectonically distinct 颞下部脸部斑块在组织结构上截然不同

IF 8.8 1区生物学

Cell reports Pub Date : 2024-09-12 DOI: 10.1016/j.celrep.2024.114732

Hiroki Oishi, Vladimir K. Berezovskii, Margaret S. Livingstone, Kevin S. Weiner, Michael J. Arcaro

引用次数: 0

Key roles of C2/GAP domains in SYNGAP1-related pathophysiology C2/GAP 结构域在 SYNGAP1 相关病理生理学中的关键作用

IF 8.8 1区生物学

Cell reports Pub Date : 2024-09-12 DOI: 10.1016/j.celrep.2024.114733

Danai Katsanevaki, Sally M. Till, Ingrid Buller-Peralta, Mohammad Sarfaraz Nawaz, Susana R. Louros, Vijayakumar Kapgal, Shashank Tiwari, Darren Walsh, Natasha J. Anstey, Nina G. Petrović, Alison Cormack, Vanesa Salazar-Sanchez, Anjanette Harris, William Farnworth-Rowson, Andrew Sutherland, Thomas C. Watson, Siyan Dimitrov, Adam D. Jackson, Daisy Arkell, Suryanarayan Biswal, Peter C. Kind

{"title":"Key roles of C2/GAP domains in SYNGAP1-related pathophysiology","authors":"Danai Katsanevaki, Sally M. Till, Ingrid Buller-Peralta, Mohammad Sarfaraz Nawaz, Susana R. Louros, Vijayakumar Kapgal, Shashank Tiwari, Darren Walsh, Natasha J. Anstey, Nina G. Petrović, Alison Cormack, Vanesa Salazar-Sanchez, Anjanette Harris, William Farnworth-Rowson, Andrew Sutherland, Thomas C. Watson, Siyan Dimitrov, Adam D. Jackson, Daisy Arkell, Suryanarayan Biswal, Peter C. Kind","doi":"10.1016/j.celrep.2024.114733","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114733","url":null,"abstract":"Mutations in SYNGAP1 are a common genetic cause of intellectual disability (ID) and a risk factor for autism. SYNGAP1 encodes a synaptic GTPase-activating protein (GAP) that has both signaling and scaffolding roles. Most pathogenic variants of SYNGAP1 are predicted to result in haploinsufficiency. However, some affected individuals carry missense mutations in its calcium/lipid binding (C2) and GAP domains, suggesting that many clinical features result from loss of functions carried out by these domains. To test this hypothesis, we targeted the exons encoding the C2 and GAP domains of SYNGAP. Rats heterozygous for this deletion exhibit reduced exploration and fear extinction, altered social investigation, and spontaneous seizures—key phenotypes shared with Syngap heterozygous null rats. Together, these findings indicate that the reduction of SYNGAP C2/GAP domain function is a main feature of SYNGAP haploinsufficiency. This rat model provides an important system for the study of ID, autism, and epilepsy.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222215","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

Structural insight into the Arabidopsis vacuolar anion channel ALMT9 shows clade specificity 拟南芥液泡阴离子通道 ALMT9 的结构洞察显示了支系特异性

IF 8.8 1区生物学

Cell reports Pub Date : 2024-09-12 DOI: 10.1016/j.celrep.2024.114731

Dandan Qian, Yaru Chai, Weiping Li, Bin Cui, Shaoquan Lin, Zhibin Wang, Chongyuan Wang, Le Qing Qu, Deshun Gong

{"title":"Structural insight into the Arabidopsis vacuolar anion channel ALMT9 shows clade specificity","authors":"Dandan Qian, Yaru Chai, Weiping Li, Bin Cui, Shaoquan Lin, Zhibin Wang, Chongyuan Wang, Le Qing Qu, Deshun Gong","doi":"10.1016/j.celrep.2024.114731","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114731","url":null,"abstract":"The Arabidopsis thaliana aluminum-activated malate transporter 9 (AtALMT9) functions as a vacuolar chloride channel that regulates the stomatal aperture. Here, we present the cryoelectron microscopy (cryo-EM) structures of AtALMT9 in three distinct states. AtALMT9 forms a dimer, and the pore is lined with four positively charged rings. The apo-AtALMT9 state shows a putative endogenous citrate obstructing the pore, where two W120 constriction residues enclose a gate with a pore radius of approximately 1.8 Å, representing an open state. Interestingly, channel closure is solely controlled by W120. Compared to wild-type plants, the W120A mutant exhibits more sensitivity to drought stress and is unable to restore the visual phenotype on leaves upon water recovery, reflecting persistent stomatal opening. Furthermore, notable variations are noted in channel gating and substrate recognition of Glycine max ALMT12, AtALMT9, and AtALMT1. In summary, our investigation enhances comprehension of the interplay between structure and function within the ALMT family.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222217","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

A nature-inspired HIF stabilizer derived from a highland-adaptation insertion of plateau pika Epas1 protein 从高原鼠兔 Epas1 蛋白的高原适应插入物中提取的自然启发型 HIF 稳定剂

IF 8.8 1区生物学

Cell reports Pub Date : 2024-09-12 DOI: 10.1016/j.celrep.2024.114727

Ziqing Yu, Guangdi Ran, Juan Chai, Eric Erquan Zhang

{"title":"A nature-inspired HIF stabilizer derived from a highland-adaptation insertion of plateau pika Epas1 protein","authors":"Ziqing Yu, Guangdi Ran, Juan Chai, Eric Erquan Zhang","doi":"10.1016/j.celrep.2024.114727","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114727","url":null,"abstract":"Hypoxia-inducible factors (HIFs) play pivotal roles in numerous diseases and high-altitude adaptation, and HIF stabilizers have emerged as valuable therapeutic tools. In our prior investigation, we identified a highland-adaptation 24-amino-acid insertion within the Epas1 protein. This insertion enhances the protein stability of Epas1, and mice engineered with this insertion display enhanced resilience to hypoxic conditions. In the current study, we delved into the biochemical mechanisms underlying the protein-stabilizing effects of this insertion. Our findings unveiled that the last 11 amino acids within this insertion adopt a helical conformation and interact with the α-domain of the von Hippel-Lindau tumor suppressor protein (pVHL), thereby disrupting the Eloc-pVHL interaction and impeding the ubiquitination of Epas1. Utilizing a synthesized peptide, E14–24, we demonstrated its favorable membrane permeability and ability to stabilize endogenous HIF-α proteins, inducing the expression of hypoxia-responsive element (HRE) genes. Furthermore, the administration of E14–24 to mice subjected to hypoxic conditions mitigated body weight loss, suggesting its potential to enhance hypoxia adaptation.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222213","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