Cell reports最新文献_第7页

Prefrontal multistimulus integration within a dedicated disambiguation circuit guides interleaving contingency judgment learning. 前额叶多刺激整合在专用消歧回路中，引导交错权变判断学习。

IF 7.5 1区生物学

Cell reports Pub Date : 2024-10-29 DOI: 10.1016/j.celrep.2024.114926

Justin D Pastore, Johannes Mayer, Jordan Steinhauser, Kylene Shuler, Tyler W Bailey, John H Speigel, Evangelos E Papalexakis, Edward Korzus

{"title":"Prefrontal multistimulus integration within a dedicated disambiguation circuit guides interleaving contingency judgment learning.","authors":"Justin D Pastore, Johannes Mayer, Jordan Steinhauser, Kylene Shuler, Tyler W Bailey, John H Speigel, Evangelos E Papalexakis, Edward Korzus","doi":"10.1016/j.celrep.2024.114926","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114926","url":null,"abstract":"Understanding how cortical network dynamics support learning is a challenge. This study investigates the role of local neural mechanisms in the prefrontal cortex during contingency judgment learning (CJL). To better understand brain network mechanisms underlying CJL, we introduce ambiguity into associative learning after fear acquisition, inducing a generalized fear response to an ambiguous stimulus sharing nontrivial similarities with the conditioned stimulus. Real-time recordings at single-neuron resolution from the prelimbic (PL) cortex show distinct PL network dynamics across CJL phases. Fear acquisition triggers PL network reorganization, led by a disambiguation circuit managing spurious and predictive relationships during cue-danger, cue-safety, and cue-neutrality contingencies. Mice with PL-targeted memory deficiency show malfunctioning disambiguation circuit function, while naive mice lacking unconditioned stimulus exposure lack the disambiguation circuit. This study shows that fear conditioning induces prefrontal cortex cognitive map reorganization and that subsequent CJL relies on the disambiguation circuit's ability to learn predictive relationships.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 11","pages":"114926"},"PeriodicalIF":7.5,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543947","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

NUP98 fusion proteins and KMT2A-MENIN antagonize PRC1.1 to drive gene expression in AML. NUP98 融合蛋白和 KMT2A-MENIN 可拮抗 PRC1.1，从而驱动 AML 中的基因表达。

IF 7.5 1区生物学

Cell reports Pub Date : 2024-10-29 DOI: 10.1016/j.celrep.2024.114901

Emily B Heikamp, Cynthia Martucci, Jill A Henrich, Dana S Neel, Sanisha Mahendra-Rajah, Hannah Rice, Daniela V Wenge, Florian Perner, Yanhe Wen, Charlie Hatton, Scott A Armstrong

{"title":"NUP98 fusion proteins and KMT2A-MENIN antagonize PRC1.1 to drive gene expression in AML.","authors":"Emily B Heikamp, Cynthia Martucci, Jill A Henrich, Dana S Neel, Sanisha Mahendra-Rajah, Hannah Rice, Daniela V Wenge, Florian Perner, Yanhe Wen, Charlie Hatton, Scott A Armstrong","doi":"10.1016/j.celrep.2024.114901","DOIUrl":"10.1016/j.celrep.2024.114901","url":null,"abstract":"Control of stem cell-associated genes by Trithorax group (TrxG) and Polycomb group (PcG) proteins is frequently misregulated in cancer. In leukemia, oncogenic fusion proteins hijack the TrxG homolog KMT2A and disrupt PcG activity to maintain pro-leukemogenic gene expression, though the mechanisms by which oncofusion proteins antagonize PcG proteins remain unclear. Here, we define the relationship between NUP98 oncofusion proteins and the non-canonical polycomb repressive complex 1.1 (PRC1.1) in leukemia using Menin-KMT2A inhibitors and targeted degradation of NUP98 fusion proteins. Eviction of the NUP98 fusion-Menin-KMT2A complex from chromatin is not sufficient to silence pro-leukemogenic genes. In the absence of PRC1.1, key oncogenes remain transcriptionally active. Transition to a repressed chromatin state requires the accumulation of PRC1.1 and repressive histone modifications. We show that PRC1.1 loss leads to resistance to small-molecule Menin-KMT2A inhibitors in vivo. Therefore, a critical function of oncofusion proteins that hijack Menin-KMT2A activity is antagonizing repressive chromatin complexes.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 11","pages":"114901"},"PeriodicalIF":7.5,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543945","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

Alternative isoforms and phase separation of Ref1 repress morphogenesis in Cryptococcus. Ref1 的替代异构体和相分离抑制了隐球菌的形态发生。

IF 7.5 1区生物学

Cell reports Pub Date : 2024-10-29 DOI: 10.1016/j.celrep.2024.114904

Nathan K Glueck, Xiaofeng Xie, Xiaorong Lin

引用次数: 0

Highly neurogenic glia from human and mouse myenteric ganglia generate functional neurons following culture and transplantation into the gut. 来自人类和小鼠肠系膜神经节的高神经源胶质细胞经过培养并移植到肠道后会产生功能性神经元。

IF 7.5 1区生物学

Cell reports Pub Date : 2024-10-28 DOI: 10.1016/j.celrep.2024.114919

Jessica L Mueller, Abigail R Leavitt, Ahmed A Rahman, Christopher Y Han, Leah C Ott, Narges S Mahdavian, Simona E Carbone, Sebastian K King, Alan J Burns, Daniel P Poole, Ryo Hotta, Allan M Goldstein, Rhian Stavely

{"title":"Highly neurogenic glia from human and mouse myenteric ganglia generate functional neurons following culture and transplantation into the gut.","authors":"Jessica L Mueller, Abigail R Leavitt, Ahmed A Rahman, Christopher Y Han, Leah C Ott, Narges S Mahdavian, Simona E Carbone, Sebastian K King, Alan J Burns, Daniel P Poole, Ryo Hotta, Allan M Goldstein, Rhian Stavely","doi":"10.1016/j.celrep.2024.114919","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114919","url":null,"abstract":"Enteric neural stem cell (ENSC) therapy offers great promise for neurointestinal diseases; however, current isolation methods yield insufficient neurons for regenerative applications. Multiomic profiling of enteric glial cells (EGCs) suggests that subpopulations within myenteric ganglia (MyGa) are a reservoir of highly neurogenic ENSCs. Here, we describe protocols to enrich for intraganglionic EGCs by isolating intact fragments of MyGa, generating cultures with higher neuronal purity than traditional methodologies isolating intramuscular single cells (IM-SCs). MyGa-derived EGCs transdifferentiate into more neurons than IM-SC-derived EGCs do, confirming their neurogenic predisposition. Following transplantation to the mouse intestine, MyGa-derived neurons generate calcium transients and activate smooth muscle in response to optogenetic stimulation. In the human intestine, MyGa-derived cells are similarly highly neurogenic, are enriched for a distinct progenitor population identified by single-cell RNA sequencing (scRNA-seq), and exhibit neuromuscular connectivity following xenogeneic transplantation into mice. Highly neurogenic ENSCs are preferentially located within the MyGa, and their selective isolation offers considerable potential for therapy.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 11","pages":"114919"},"PeriodicalIF":7.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543943","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

Shared signals, different fates: Calcium and ROS in plant PRR and NLR immunity. 共同的信号，不同的命运：植物 PRR 和 NLR 免疫中的钙和 ROS。

IF 7.5 1区生物学

Cell reports Pub Date : 2024-10-28 DOI: 10.1016/j.celrep.2024.114910

Chanusha Weralupitiya, Sophie Eccersall, Claudia-Nicole Meisrimler

引用次数: 0

PD-1 endocytosis unleashes the cytolytic potential of checkpoint blockade in tumor immunity. PD-1 内吞释放了检查点阻断在肿瘤免疫中的细胞溶解潜能。

IF 7.5 1区生物学

Cell reports Pub Date : 2024-10-28 DOI: 10.1016/j.celrep.2024.114907

Elham Ben Saad, Andres Oroya, Nikhil Ponnoor Anto, Meriem Bachais, Christopher E Rudd

{"title":"PD-1 endocytosis unleashes the cytolytic potential of checkpoint blockade in tumor immunity.","authors":"Elham Ben Saad, Andres Oroya, Nikhil Ponnoor Anto, Meriem Bachais, Christopher E Rudd","doi":"10.1016/j.celrep.2024.114907","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114907","url":null,"abstract":"PD-1 immune checkpoint blockade (ICB) is a key cancer treatment. While blocking PD-1 binding to ligand is known, the role of internalization in enhancing ICB efficacy is less explored. Our study reveals that PD-1 internalization helps unlock ICB's full potential in cancer immunotherapy. Anti-PD-1 induces 50%-60% surface PD-1 internalization from human and mouse cells, leaving low to intermediate levels of resistant receptors. Complexes then appear in early and late endosomes. Both CD4 and CD8 T cells, especially CD8+ effectors, are affected. Nivolumab outperforms pembrolizumab in human T cells, while PD-1 internalization requires crosslinking by bivalent antibody. While mono- and bivalent anti-PD-1 inhibit tumor growth with CD8 tumor-infiltrating cells expressing increased granzyme B, bivalent antibody is more effective where the combination of steric blockade and endocytosis induces greater CD8+ T cell tumor infiltration and the expression of the cytolytic pore protein, perforin. Our findings highlight an ICB mechanism that combines steric blockade and PD-1 endocytosis for optimal checkpoint immunotherapy.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 11","pages":"114907"},"PeriodicalIF":7.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543946","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

Nanoparticle-based itaconate treatment recapitulates low-cholesterol/low-fat diet-induced atherosclerotic plaque resolution. 基于纳米颗粒的伊他康酸治疗可重现低胆固醇/低脂饮食诱导的动脉粥样硬化斑块消退。

IF 7.5 1区生物学

Cell reports Pub Date : 2024-10-27 DOI: 10.1016/j.celrep.2024.114911

Natalie E Hong, Alice Chaplin, Lin Di, Anastasia Ravodina, Graham H Bevan, Huiyun Gao, Courteney Asase, Roopesh Singh Gangwar, Mark J Cameron, Matthew Mignery, Olga Cherepanova, Aloke V Finn, Lalitha Nayak, Andrew A Pieper, Andrei Maiseyeu

{"title":"Nanoparticle-based itaconate treatment recapitulates low-cholesterol/low-fat diet-induced atherosclerotic plaque resolution.","authors":"Natalie E Hong, Alice Chaplin, Lin Di, Anastasia Ravodina, Graham H Bevan, Huiyun Gao, Courteney Asase, Roopesh Singh Gangwar, Mark J Cameron, Matthew Mignery, Olga Cherepanova, Aloke V Finn, Lalitha Nayak, Andrew A Pieper, Andrei Maiseyeu","doi":"10.1016/j.celrep.2024.114911","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114911","url":null,"abstract":"Current pharmacologic treatments for atherosclerosis do not completely protect patients; additional protection can be achieved by dietary modifications, such as a low-cholesterol/low-fat diet (LCLFD), that mediate plaque stabilization and inflammation reduction. However, this lifestyle modification can be challenging for patients. Unfortunately, incomplete understanding of the underlying mechanisms has thwarted efforts to mimic the protective effects of a LCLFD. Here, we report that the tricarboxylic acid cycle intermediate itaconate (ITA), produced by plaque macrophages, is key to diet-induced plaque resolution. ITA is produced by immunoresponsive gene 1 (IRG1), which we observe is highly elevated in myeloid cells of vulnerable plaques and absent from early or stable plaques in mice and humans. We additionally report development of an ITA-conjugated lipid nanoparticle that accumulates in plaque and bone marrow myeloid cells, epigenetically reduces inflammation via H3K27ac deacetylation, and reproduces the therapeutic effects of LCLFD-induced plaque resolution in multiple atherosclerosis models.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 11","pages":"114911"},"PeriodicalIF":7.5,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521150","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

CD84 as a therapeutic target for breaking immune tolerance in triple-negative breast cancer. 将 CD84 作为打破三阴性乳腺癌免疫耐受的治疗靶点。

IF 7.5 1区生物学

Cell reports Pub Date : 2024-10-27 DOI: 10.1016/j.celrep.2024.114920

Stav Rabani, Emine Gulsen Gunes, Martin Gunes, Bianca Pellegrino, Bar Lampert, Keren David, Raju Pillai, Aimin Li, Shirly Becker-Herman, Steven T Rosen, Idit Shachar

引用次数: 0

Extracellular vesicle-packaged PD-L1 impedes macrophage-mediated antibacterial immunity in preexisting malignancy. 细胞外囊泡包装的PD-L1会阻碍巨噬细胞介导的先期恶性肿瘤抗菌免疫。

IF 7.5 1区生物学

Cell reports Pub Date : 2024-10-26 DOI: 10.1016/j.celrep.2024.114903

He-Jing Zhang, Lingxin Zhu, Qi-Hui Xie, Lin-Zhou Zhang, Jin-Yuan Liu, Yang-Ying-Fan Feng, Zhuo-Kun Chen, Hou-Fu Xia, Qiu-Yun Fu, Zi-Li Yu, Gang Chen

{"title":"Extracellular vesicle-packaged PD-L1 impedes macrophage-mediated antibacterial immunity in preexisting malignancy.","authors":"He-Jing Zhang, Lingxin Zhu, Qi-Hui Xie, Lin-Zhou Zhang, Jin-Yuan Liu, Yang-Ying-Fan Feng, Zhuo-Kun Chen, Hou-Fu Xia, Qiu-Yun Fu, Zi-Li Yu, Gang Chen","doi":"10.1016/j.celrep.2024.114903","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114903","url":null,"abstract":"Malignancies can compromise systemic innate immunity, but the underlying mechanisms are largely unknown. Here, we find that tumor-derived small extracellular vesicles (sEVs; TEVs) deliver PD-L1 to host macrophages, thereby impeding antibacterial immunity. Mice implanted with Rab27a-knockdown tumors are more resistant to bacterial infection than wild-type controls. Injection of TEVs into mice impairs macrophage-mediated bacterial clearance, increases systemic bacterial dissemination, and enhances sepsis score in a PD-L1-dependent manner. Mechanistically, TEV-packaged PD-L1 inhibits Bruton's tyrosine kinase/PLCγ2 signaling-mediated cytoskeleton reorganization and reactive oxygen species generation, impacting bacterial phagocytosis and killing by macrophages. Neutralizing PD-L1 markedly normalizes macrophage-mediated bacterial clearance in tumor-bearing mice. Importantly, circulating sEV PD-L1 levels in patients with tumors can predict bacterial infection susceptibility, while patients with tumors treated with αPD-1 exhibit fewer postoperative infections. These findings identify a mechanism by which cancer cells dampen host innate immunity-mediated bacterial clearance and suggest targeting TEV-packaged PD-L1 to reduce bacterial infection susceptibility in tumor-bearing conditions.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 11","pages":"114903"},"PeriodicalIF":7.5,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567443","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

Defects in CYB5A and CYB5B impact sterol-C4 oxidation in cholesterol biosynthesis and demonstrate regulatory roles of dimethyl sterols. CYB5A 和 CYB5B 的缺陷会影响胆固醇生物合成过程中固醇-C4 的氧化，并显示出二甲基固醇的调节作用。

IF 7.5 1区生物学

Cell reports Pub Date : 2024-10-26 DOI: 10.1016/j.celrep.2024.114912

Mei-Yan Ma, Gang Deng, Wen-Zhuo Zhu, Ming Sun, Lu-Yi Jiang, Wei-Hui Li, Yuan-Bin Liu, Lin Guo, Bao-Liang Song, Xiaolu Zhao

{"title":"Defects in CYB5A and CYB5B impact sterol-C4 oxidation in cholesterol biosynthesis and demonstrate regulatory roles of dimethyl sterols.","authors":"Mei-Yan Ma, Gang Deng, Wen-Zhuo Zhu, Ming Sun, Lu-Yi Jiang, Wei-Hui Li, Yuan-Bin Liu, Lin Guo, Bao-Liang Song, Xiaolu Zhao","doi":"10.1016/j.celrep.2024.114912","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114912","url":null,"abstract":"Cytochrome b5 (CYB5) is a hemoprotein crucial for electron transfer to oxygenases. Although microsomal CYB5A is required for sterol C4-demethylation in vitro, cholesterol biosynthesis remains intact in Cyb5a knockout mice. Here, we show that knockout of mitochondrial CYB5B, rather than CYB5A, blocks cholesterol biosynthesis at the sterol-C4 oxidation step in HeLa cells, causing an accumulation of testis meiosis-activating sterol (T-MAS) and dihydro-T-MAS. Surprisingly, liver-specific Cyb5b knockout (L-Cyb5b-/-) mice exhibit normal cholesterol metabolism. Further knockdown of Cyb5a in L-Cyb5b-/- (L-Cyb5b-/-/short hairpin [sh]Cyb5a) mice leads to a marked accumulation of T-MAS and dihydro-T-MAS, indicating that either CYB5A or CYB5B is required for sterol C4-demethylation. The L-Cyb5b-/-/shCyb5a mice are largely normal, with lower sterol regulatory element-binding protein (SREBP)-target gene expression during refeeding and higher liver triglyceride levels while fasting, as T-MAS and dihydro-T-MAS inhibit the SREBP pathway and activate the PPARγ pathway. In summary, CYB5A and CYB5B compensate for sterol C4-demethylation, and T-MAS and dihydro-T-MAS can modulate the SREBP and PPARγ pathways.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 11","pages":"114912"},"PeriodicalIF":7.5,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567442","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