{"title":"NFE2-driven neutrophil polarization promotes pancreatic cancer liver metastasis progression.","authors":"Wenchao Xu, Jianzhou Liu, Qiaofei Liu, Jia Xu, Li Zhou, Zhiyong Liang, Haoran Huang, Bowen Huang, Gary Guishan Xiao, Junchao Guo","doi":"10.1016/j.celrep.2024.115226","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.115226","url":null,"abstract":"<p><p>Pancreatic cancer liver metastasis is an important factor leading to dismal prognoses. The details of adaptive immune remodeling in liver metastasis, especially the role of neutrophils, remain elusive. Here, combined single-cell sequencing with spatial transcriptomics results revealed that liver metastases exhibit more aggressive transcriptional characteristics and higher levels of immunosuppression compared with the primary tumor. We identified neutrophils_S100A12 (S100 calcium binding protein A12) cells as the pivotal pro-metastatic cluster, specifically distributed at the invasive front of the metastatic lesions. Mechanistically, our findings indicated that nuclear factor erythroid 2 (NFE2) is a key transcription factor regulating neutrophil phenotypic polarization. Metastatic tumors produce transforming growth factor β to activate the SMAD3 pathway within neutrophils, inducing NFE2-driven polarization. NFE2 promotes the transcription of peptidylarginine deiminase 4 by binding to its promoter, leading to the generation of neutrophil extracellular traps at the invasive front. Collectively, our data demonstrate that NFE2-driven neutrophil polarization is a potential target for anti-metastatic therapy.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 2","pages":"115226"},"PeriodicalIF":7.5,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000844","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}
Cell reportsPub Date : 2025-01-18DOI: 10.1016/j.celrep.2025.115257
Severin J Schink, Zara Gough, Elena Biselli, Mariel Garcia Huiman, Yu-Fang Chang, Markus Basan, Ulrich Gerland
{"title":"MetA is a ''thermal fuse'' that inhibits growth and protects Escherichia coli at elevated temperatures.","authors":"Severin J Schink, Zara Gough, Elena Biselli, Mariel Garcia Huiman, Yu-Fang Chang, Markus Basan, Ulrich Gerland","doi":"10.1016/j.celrep.2025.115257","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115257","url":null,"abstract":"","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 1","pages":"115257"},"PeriodicalIF":7.5,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000782","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}
Cell reportsPub Date : 2025-01-18DOI: 10.1016/j.celrep.2024.115225
Leonardo Matta, Peter Weber, Suheda Erener, Alina Walth-Hummel, Daniela Hass, Lea K Bühler, Katarina Klepac, Julia Szendroedi, Joel Guerra, Maria Rohm, Michael Sterr, Heiko Lickert, Alexander Bartelt, Stephan Herzig
{"title":"Chronic intermittent fasting impairs β cell maturation and function in adolescent mice.","authors":"Leonardo Matta, Peter Weber, Suheda Erener, Alina Walth-Hummel, Daniela Hass, Lea K Bühler, Katarina Klepac, Julia Szendroedi, Joel Guerra, Maria Rohm, Michael Sterr, Heiko Lickert, Alexander Bartelt, Stephan Herzig","doi":"10.1016/j.celrep.2024.115225","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.115225","url":null,"abstract":"<p><p>Intermittent fasting (IF) is a nutritional lifestyle intervention with broad metabolic benefits, but whether the impact of IF depends on the individual's age is unclear. Here, we investigated the effects of IF on systemic metabolism and β cell function in old, middle-aged, and young mice. Short-term IF improves glucose homeostasis across all age groups without altering islet function and morphology. In contrast, while chronic IF is beneficial for adult mice, it results in impaired β cell function in the young. Using single-cell RNA sequencing (scRNA-seq), we delineate that the β cell maturation and function scores are reduced in young mice. In human islets, a similar pattern is observed in type 1 (T1D), but not type 2 (T2D), diabetes, suggesting that the impact of chronic IF in adolescence is linked to the development of β cell dysfunction. Our study suggests considering the duration of IF in younger persons, as it may worsen rather than reduce diabetes outcomes.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 2","pages":"115225"},"PeriodicalIF":7.5,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000841","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}
Cell reportsPub Date : 2025-01-18DOI: 10.1016/j.celrep.2025.115244
Kathrin Maedler, Heena Pahwa
{"title":"The adult table: Chronic intermittent fasting improves β cell health only in adults.","authors":"Kathrin Maedler, Heena Pahwa","doi":"10.1016/j.celrep.2025.115244","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115244","url":null,"abstract":"<p><p>Intermittent fasting (IF) improves metabolic health in some individuals but increases health risks in others. Matta et al. now show that IF oppositely affects β cells depending on age: beneficial at old but deleterious at young age.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 2","pages":"115244"},"PeriodicalIF":7.5,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000847","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}
{"title":"TWEAK-Fn14 signaling protects mice from pulmonary fibrosis by inhibiting fibroblast activation and recruiting pro-regenerative macrophages.","authors":"Li Liu, Pei Wu, Yuqi Wei, Meng Lu, Haiyan Ge, Ping Wang, Jianlong Sun, Tiffany Horng, Xiucheng Liu, Xiaoyong Shen, Lingyun Sun, Ying Xi","doi":"10.1016/j.celrep.2024.115220","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.115220","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by excess accumulation of the extracellular matrix (ECM). The role of macrophage-fibroblast crosstalk in lung fibrogenesis is incompletely understood. Here we found that fibroblast growth factor-inducible molecule 14 (Fn14), the receptor for tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is highly induced in myofibroblasts in the lungs of IPF patients and the bleomycin-induced lung fibrosis model. TWEAK-Fn14 signaling inhibits fibroblast activation and ECM synthesis and induces chemokine expression to recruit monocytes/macrophages into the lung. Fn14 deficiency increases ECM production and impairs macrophage infiltration and differentiation, leading to exacerbated lung fibrosis and impaired alveolar regeneration in a bleomycin model. Interestingly, Fn14 deficiency diminishes an injury-induced SiglecF<sup>-</sup> CD11b<sup>-</sup> MHCII<sup>lo</sup> intermediate macrophage (IntermM) subpopulation, which promotes alveolar type II (AT2) cell proliferation in organoid cultures. These results collectively demonstrate a protective role of TWEAK-Fn14 signaling in lung fibrosis, highlighting the complexities and multilayered regulation of macrophage-fibroblast crosstalk.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 2","pages":"115220"},"PeriodicalIF":7.5,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000792","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}
Cell reportsPub Date : 2025-01-17DOI: 10.1016/j.celrep.2025.115252
Kun D Huang, Mattea Müller, Pavaret Sivapornnukul, Agata Anna Bielecka, Lena Amend, Caroline Tawk, Anja Bruns, Till-Robin Lesker, Andreas Hahn, Till Strowig
{"title":"Dietary selective effects manifest in the human gut microbiota from species composition to strain genetic makeup.","authors":"Kun D Huang, Mattea Müller, Pavaret Sivapornnukul, Agata Anna Bielecka, Lena Amend, Caroline Tawk, Anja Bruns, Till-Robin Lesker, Andreas Hahn, Till Strowig","doi":"10.1016/j.celrep.2025.115252","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115252","url":null,"abstract":"","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 1","pages":"115252"},"PeriodicalIF":7.5,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000732","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}
Cell reportsPub Date : 2025-01-17DOI: 10.1016/j.celrep.2024.115214
Ning Zhou, Jingchen Yu, Xujiao Liu, Chengxi Li, Huang Tang, Lin Lyu, Chengwei Wu, Yana Chen, Jian Zhang, Jinjing Ni, Danni Wang, Jing Tao, Wenjuan Wu, Yu Zhang, Yun Feng, Yanjie Chao, Jie Lu, Ping He, Yu-Feng Yao
{"title":"Within-host evolution of a transcriptional regulator contributes to the establishment of chronic Pseudomonas aeruginosa infection.","authors":"Ning Zhou, Jingchen Yu, Xujiao Liu, Chengxi Li, Huang Tang, Lin Lyu, Chengwei Wu, Yana Chen, Jian Zhang, Jinjing Ni, Danni Wang, Jing Tao, Wenjuan Wu, Yu Zhang, Yun Feng, Yanjie Chao, Jie Lu, Ping He, Yu-Feng Yao","doi":"10.1016/j.celrep.2024.115214","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.115214","url":null,"abstract":"<p><p>As an opportunistic pathogen, Pseudomonas aeruginosa can cause both acute and chronic infections that are notoriously difficult to treat. However, the mechanism underlying acute or chronic P. aeruginosa infection remains unclear. Here, we identify a mutation in a transcriptional regulator PA5438 (named GavR). This mutation causes a 3-amino-acid absence in GavR and is strongly associated with chronic P. aeruginosa infection. Mechanistically, the deletion in GavR directly downregulates the transcription of the aceEF operon and leads to an accumulation of intracellular pyruvate, which can promote bacterial survival in neutrophils. Notably, P. aeruginosa with 9-bp-deleted or full-length gavR composes a mixed population in most patients with chronic or acute infections. Overall, the mutation in gavR attenuates P. aeruginosa virulence and enhances innate immune evasion by reprogramming pyruvate metabolism and the glyoxylate cycle. This work reveals a molecular mechanism of transition control from acute to chronic infection in P. aeruginosa.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 1","pages":"115214"},"PeriodicalIF":7.5,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000837","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}
Cell reportsPub Date : 2025-01-17DOI: 10.1016/j.celrep.2024.115223
Rosemarie D Mason, Baoshan Zhang, Nicholas C Morano, Chen-Hsiang Shen, Krisha McKee, Ashley Heimann, Renguang Du, Alexandra F Nazzari, Shelby Hodges, Tapan Kanai, Bob C Lin, Mark K Louder, Nicole A Doria-Rose, Tongqing Zhou, Lawrence Shapiro, Mario Roederer, Peter D Kwong, Jason Gorman
{"title":"Structural development of the HIV-1 apex-directed PGT145-PGDM1400 antibody lineage.","authors":"Rosemarie D Mason, Baoshan Zhang, Nicholas C Morano, Chen-Hsiang Shen, Krisha McKee, Ashley Heimann, Renguang Du, Alexandra F Nazzari, Shelby Hodges, Tapan Kanai, Bob C Lin, Mark K Louder, Nicole A Doria-Rose, Tongqing Zhou, Lawrence Shapiro, Mario Roederer, Peter D Kwong, Jason Gorman","doi":"10.1016/j.celrep.2024.115223","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.115223","url":null,"abstract":"<p><p>Broadly neutralizing antibodies (bNAbs) targeting the apex of the HIV-1-envelope (Env) trimer comprise the most potent category of HIV-1 bNAbs and have emerged as promising therapeutics. Here, we investigate the development of the HIV-1 apex-directed PGT145-PGDM1400 antibody lineage and report cryo-EM structures at 3.4 Å resolution of PGDM1400 and of an improved PGT145 variant (PGT145-R100aS), each bound to the BG505 Env trimer. Cross-species-based engineering improves PGT145 IC<sub>80</sub> breadth to near that of PGDM1400. Despite similar breadth and potency, the two antibodies differ in their residue-level interactions with important apex features, including N160 glycans and apex cavity, with residue 100i of PGT145 (sulfated tyrosine) penetrating ∼7 Å farther than residue 100i of PGDM1400 (aspartic acid). While apex-directed bNAbs from other donors use maturation pathways that often converge on analogous residue-level recognition, our results demonstrate that divergent residue-level recognition can occur within the same lineage, thereby enabling improved coverage of escape variants.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 1","pages":"115223"},"PeriodicalIF":7.5,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000755","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}
Cell reportsPub Date : 2025-01-17DOI: 10.1016/j.celrep.2024.115207
Young Hye Kwon, Joseph J Salvo, Nathan L Anderson, Donnisa Edmonds, Ania M Holubecki, Maya Lakshman, Kwangsun Yoo, B T Thomas Yeo, Kendrick Kay, Caterina Gratton, Rodrigo M Braga
{"title":"Situating the salience and parietal memory networks in the context of multiple parallel distributed networks using precision functional mapping.","authors":"Young Hye Kwon, Joseph J Salvo, Nathan L Anderson, Donnisa Edmonds, Ania M Holubecki, Maya Lakshman, Kwangsun Yoo, B T Thomas Yeo, Kendrick Kay, Caterina Gratton, Rodrigo M Braga","doi":"10.1016/j.celrep.2024.115207","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.115207","url":null,"abstract":"<p><p>Brain networks serving higher cognitive functions are widely distributed across frontal and posterior association zones. Two exceptions have been the parietal memory network (PMN) and salience network (SAL), which are typically restricted to posterior (e.g., posterior cingulate and lateral parietal cortex) and anterior (medial prefrontal and anterior insular cortex) areas, respectively. Using high-resolution neuroimaging, we show that individualized estimates of the PMN extend beyond the posterior set and encompass frontal and insula regions canonically ascribed to the SAL. This suggests that the SAL and PMN form a unified network: \"SAL/PMN.\" Task-based analyses confirm that both anterior and posterior components of the SAL/PMN show recognition-related activity. Comparison of 3T and 7T data suggests that high-resolution data more readily revealed the unified network, underscoring the importance of fine-scale distinctions for veridical representation of brain networks. Importantly, the unified network better matches the expected parallel distributed network organization that is characteristic of association cortex.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 1","pages":"115207"},"PeriodicalIF":7.5,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000752","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}
Cell reportsPub Date : 2025-01-16DOI: 10.1016/j.celrep.2024.115216
Felicia Hui Min Chan, Hui Wen Yeap, Zonghan Liu, Safwah Nasuha Rosli, Kay En Low, Isabelle Bonne, Yixuan Wu, Shu Zhen Chong, Kaiwen W Chen
{"title":"Plasticity of cell death pathways ensures GSDMD activation during Yersinia pseudotuberculosis infection.","authors":"Felicia Hui Min Chan, Hui Wen Yeap, Zonghan Liu, Safwah Nasuha Rosli, Kay En Low, Isabelle Bonne, Yixuan Wu, Shu Zhen Chong, Kaiwen W Chen","doi":"10.1016/j.celrep.2024.115216","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.115216","url":null,"abstract":"<p><p>Macrophages express pattern recognition and cytokine receptors that mediate proinflammatory signal transduction pathways to combat microbial infection. To retaliate against such responses, pathogenic microorganisms have evolved multiple strategies to impede innate immune signaling. Recent studies demonstrated that YopJ suppression of TAK1 signaling during Yersinia pseudotuberculosis infection promotes the assembly of a RIPK1-dependent death-inducing complex that enables caspase-8 to directly cleave and activate gasdermin D (GSDMD). However, whether and how macrophages respond to Yersinia infection in the absence of YopJ or caspase-8 activity remains unclear. Here, we demonstrate that loss of YopJ or its catalytic activity triggers non-canonical inflammasome activation in macrophages and that caspase-11 is required to restrict the bacterial burden in vivo. Under conditions of low caspase-8 activity, wild-type Y. pseudotuberculosis invades macrophages and accesses the cytosol, leading to non-canonical inflammasome activation. Thus, our study highlights the plasticity of death pathways to ensure GSDMD activation during Yersinia infection.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 1","pages":"115216"},"PeriodicalIF":7.5,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000822","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}