IF 64.5 1区生物学

Cell Pub Date : 2025-05-29 DOI: 10.1016/j.cell.2025.04.034

Alexandre P. Magalhaes, Denes Hnisz

引用次数: 0

A microbial amino-acid-conjugated bile acid, tryptophan-cholic acid, improves glucose homeostasis via the orphan receptor MRGPRE 微生物氨基酸缀合胆汁酸，色氨酸-胆酸，通过孤儿受体MRGPRE改善葡萄糖稳态

IF 64.5 1区生物学

Cell Pub Date : 2025-05-29 DOI: 10.1016/j.cell.2025.05.010

Jun Lin, Qixing Nie, Jie Cheng, Ya-Ni Zhong, Tianyao Zhang, Xiuying Zhang, Xiaoyan Ge, Yong Ding, Canyang Niu, Yuhua Gao, Kai Wang, Mingxin Gao, Xuemei Wang, Weixuan Chen, Chuyu Yun, Chuan Ye, Jinkun Xu, Weike Shaoyong, Lijun Zhang, Pan Shang, Changtao Jiang

{"title":"A microbial amino-acid-conjugated bile acid, tryptophan-cholic acid, improves glucose homeostasis via the orphan receptor MRGPRE","authors":"Jun Lin, Qixing Nie, Jie Cheng, Ya-Ni Zhong, Tianyao Zhang, Xiuying Zhang, Xiaoyan Ge, Yong Ding, Canyang Niu, Yuhua Gao, Kai Wang, Mingxin Gao, Xuemei Wang, Weixuan Chen, Chuyu Yun, Chuan Ye, Jinkun Xu, Weike Shaoyong, Lijun Zhang, Pan Shang, Changtao Jiang","doi":"10.1016/j.cell.2025.05.010","DOIUrl":"https://doi.org/10.1016/j.cell.2025.05.010","url":null,"abstract":"Recently, microbial amino-acid-conjugated bile acids (MABAs) have been found to be prevalent in human samples. However, their physiological significance is still unclear. Here, we identify tryptophan-conjugated cholic acid (Trp-CA) as the most significantly decreased MABA in patients with type 2 diabetes (T2D), and its abundance is negatively correlated with clinical glycemic markers. We further demonstrate that Trp-CA improves glucose tolerance in diabetic mice. Mechanistically, we find that Trp-CA is a ligand of the orphan G protein-coupled receptor (GPCR) Mas-related G protein-coupled receptor family member E (MRGPRE) and determine the binding mode between the two. Both MRGPRE-Gs-cyclic AMP (cAMP) and MRGPRE-β-arrestin-1-aldolase A (ALDOA) signaling pathways contribute to the metabolic benefits of Trp-CA. Additionally, we find that the bacterial bile salt hydrolase/transferase of Bifidobacterium is responsible for the production of Trp-CA. Together, our findings pave the way for further research on MABAs and offer additional therapeutic targets for the treatment of T2D.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"82 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144165310","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

The microbiome for clinicians 临床医生的微生物组

IF 64.5 1区生物学

Cell Pub Date : 2025-05-29 DOI: 10.1016/j.cell.2025.04.016

Serena Porcari, Siew C. Ng, Laurence Zitvogel, Harry Sokol, Rinse K. Weersma, Eran Elinav, Antonio Gasbarrini, Giovanni Cammarota, Herbert Tilg, Gianluca Ianiro

引用次数: 0

Extensive N4 cytosine methylation is essential for Marchantia sperm function. 广泛的N4胞嘧啶甲基化对马氏精子功能至关重要。

IF 45.5 1区生物学

Cell Pub Date : 2025-05-29 Epub Date: 2025-04-09 DOI: 10.1016/j.cell.2025.03.014

James Walker, Jingyi Zhang, Yalin Liu, Shujuan Xu, Yiming Yu, Martin Vickers, Weizhi Ouyang, Judit Tálas, Liam Dolan, Keiji Nakajima, Xiaoqi Feng

引用次数: 0

Advancing proteomic analysis for understanding disease biology and biomarker discovery 推进蛋白质组学分析，了解疾病生物学和生物标志物的发现

IF 64.5 1区生物学

Cell Pub Date : 2025-05-29 DOI: 10.1016/j.cell.2025.04.040

Carlos Cruchaga

引用次数: 0

ExSPECKt the unexpected: NLRP3-caspase-8-dependent cell death in RBCs 意想不到的：nlrp3 -caspase-8依赖性红细胞细胞死亡

IF 64.5 1区生物学

Cell Pub Date : 2025-05-29 DOI: 10.1016/j.cell.2025.04.033

Rebecca E. Tweedell, Thirumala-Devi Kanneganti

引用次数: 0

Machine-learning-assisted universal protein activation in living mice 机器学习辅助的活小鼠通用蛋白激活

IF 64.5 1区生物学

Cell Pub Date : 2025-05-27 DOI: 10.1016/j.cell.2025.05.006

Xin Wang, Yuan Liu, Zhenchao Wang, Xiangmei Zeng, William Shu Ching Ngai, Jie Wang, Heng Zhang, Xiao Xie, Rongfeng Zhu, Xinyuan Fan, Chu Wang, Peng R. Chen

{"title":"Machine-learning-assisted universal protein activation in living mice","authors":"Xin Wang, Yuan Liu, Zhenchao Wang, Xiangmei Zeng, William Shu Ching Ngai, Jie Wang, Heng Zhang, Xiao Xie, Rongfeng Zhu, Xinyuan Fan, Chu Wang, Peng R. Chen","doi":"10.1016/j.cell.2025.05.006","DOIUrl":"https://doi.org/10.1016/j.cell.2025.05.006","url":null,"abstract":"A universal strategy to precisely control protein activation in living animals is crucial for gain-of-function study of proteins under in vivo settings. We herein report CAGE-Proxvivo, a computer-aided proximal decaging strategy for on-demand protein activation as well as protein-protein interaction modulations in living mice. Through machine-learning-assisted evolution of desired aminoacyl-tRNA synthetases (aaRSs), we successfully incorporated chemically caged amino acids into rationally designed “decaging sites” to transiently block target proteins’ function, which can be restored in situ via a small-molecule-triggered bioorthogonal cleavage reaction. This method demonstrates broad applicability ranging from activating proteins of interest to cell-type-specific modulation of distinct phenotypes in living systems. Beyond the active-pocket decaging, CAGE-Proxvivo also enables precise control of protein-protein interactions, as exemplified by a “gated” anti-CD3 antibody that permits chemically regulated T cell recruitment and activation at tumor sites. Overall, CAGE-Proxvivo offers a universal platform for time-resolved biological studies and on-demand therapeutic interventions under living conditions.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"26 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145859","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

Personalized molecular signatures of insulin resistance and type 2 diabetes 胰岛素抵抗和2型糖尿病的个性化分子特征

IF 64.5 1区生物学

Cell Pub Date : 2025-05-27 DOI: 10.1016/j.cell.2025.05.005

Jeppe Kjærgaard, Ben Stocks, John Henderson, Jordana B. Freemantle, David Rizo-Roca, Michele Puglia, Maria Madrazo Montoya, Daniel Andersson, Jesper Bäckdahl, Daniel Eriksson-Hogling, Jacob V. Stidsen, Michael Wierer, Simon Rasmussen, Kei Sakamoto, Kurt Højlund, Mikael Rydén, Juleen R. Zierath, Anna Krook, Atul S. Deshmukh

{"title":"Personalized molecular signatures of insulin resistance and type 2 diabetes","authors":"Jeppe Kjærgaard, Ben Stocks, John Henderson, Jordana B. Freemantle, David Rizo-Roca, Michele Puglia, Maria Madrazo Montoya, Daniel Andersson, Jesper Bäckdahl, Daniel Eriksson-Hogling, Jacob V. Stidsen, Michael Wierer, Simon Rasmussen, Kei Sakamoto, Kurt Højlund, Mikael Rydén, Juleen R. Zierath, Anna Krook, Atul S. Deshmukh","doi":"10.1016/j.cell.2025.05.005","DOIUrl":"https://doi.org/10.1016/j.cell.2025.05.005","url":null,"abstract":"Insulin resistance is a hallmark of type 2 diabetes, which is a highly heterogeneous disease with diverse pathology. Understanding the molecular signatures of insulin resistance and its association with individual phenotypic traits is crucial for advancing precision medicine in type 2 diabetes. Utilizing cutting-edge proteomics technology, we mapped the proteome and phosphoproteome of skeletal muscle from >120 men and women with normal glucose tolerance or type 2 diabetes, with varying degrees of insulin sensitivity. Leveraging deep in vivo phenotyping, we reveal that fasting proteome and phosphoproteome signatures strongly predict insulin sensitivity. Furthermore, the insulin-stimulated phosphoproteome revealed both dysregulated and preserved signaling nodes—even in individuals with severe insulin resistance. While substantial sex-specific differences in the proteome and phosphoproteome were identified, molecular signatures of insulin resistance remained largely similar between men and women. These findings emphasize the necessity of incorporating disease heterogeneity into type 2 diabetes care strategies.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"34 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145863","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

De novo assembly of nuclear stress bodies rearranges and enhances NFIL3 to restrain acute inflammatory responses 核应激体从头组装重排并增强NFIL3以抑制急性炎症反应

IF 64.5 1区生物学

Cell Pub Date : 2025-05-27 DOI: 10.1016/j.cell.2025.05.003

Xiao-Qi Liu, Pan Li, Bao-Qing Gao, Heng-Le Zhu, Liang-Zhong Yang, Yang Wang, Yu-Yao Zhang, Hao Wu, Yu-Hang Pan, Lin Shan, Hongtao Yu, Li Yang, Ling-Ling Chen

{"title":"De novo assembly of nuclear stress bodies rearranges and enhances NFIL3 to restrain acute inflammatory responses","authors":"Xiao-Qi Liu, Pan Li, Bao-Qing Gao, Heng-Le Zhu, Liang-Zhong Yang, Yang Wang, Yu-Yao Zhang, Hao Wu, Yu-Hang Pan, Lin Shan, Hongtao Yu, Li Yang, Ling-Ling Chen","doi":"10.1016/j.cell.2025.05.003","DOIUrl":"https://doi.org/10.1016/j.cell.2025.05.003","url":null,"abstract":"The membrane-less nuclear stress bodies (nSBs), with satellite III (SatIII) RNAs as the hallmark, are present in primates upon sensing stresses. We report that SatⅢ DNAs, SatⅢ RNAs, and 30 nSB proteins assemble into well-organized structures shortly after stresses. The activated SatⅢ heterochromatin loci rapidly expand, resulting in reduced spatial distance and enhanced expression of adjacent genes, including the transcription suppressor NFIL3, which is known to dampen proinflammatory cytokine production. Rearranging NFIL3 loci within the nSB territory enhances NFIL3 chromatin accessibility and makes NFIL3 promoters more accessible to transcription factors heat shock transcription factor 1 (HSF1) and bromodomain containing 4 (BRD4), which are also recruited to nSBs upon stresses. Human peripheral blood mononuclear cell (PBMC)-derived macrophages under heat shock plus pathogen-associated molecular pattern treatments exhibit increased SatⅢ and NFIL3 expression, the latter of which suppresses key inflammatory cytokines. Importantly, NFIL3 expression positively correlates with SatⅢ activation in septic patients, a process positively correlated to patient survival, highlighting a role of nSBs in restraining inflammatory responses.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"83 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145858","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-organ metabolite production and consumption in healthy and atherogenic conditions 健康和动脉粥样硬化条件下跨器官代谢物的产生和消耗

IF 64.5 1区生物学

Cell Pub Date : 2025-05-27 DOI: 10.1016/j.cell.2025.05.001

Hosung Bae, Sunhee Jung, Johnny Le, Ian Tamburini, Joohwan Kim, Eric Wang, Won-Suk Song, Wonsuk Choi, Ki-Hong Jang, Taekyung Kang, Miranda L. Lopez, Cuauhtemoc Ramirez, Ipsita Mohanty, Miranda E. Kelly, Jessie Kim, Raymond Kim, Sang Hee Park, Jongwon Baek, Bryan Mendez, Paul Petrus, Cholsoon Jang

{"title":"Cross-organ metabolite production and consumption in healthy and atherogenic conditions","authors":"Hosung Bae, Sunhee Jung, Johnny Le, Ian Tamburini, Joohwan Kim, Eric Wang, Won-Suk Song, Wonsuk Choi, Ki-Hong Jang, Taekyung Kang, Miranda L. Lopez, Cuauhtemoc Ramirez, Ipsita Mohanty, Miranda E. Kelly, Jessie Kim, Raymond Kim, Sang Hee Park, Jongwon Baek, Bryan Mendez, Paul Petrus, Cholsoon Jang","doi":"10.1016/j.cell.2025.05.001","DOIUrl":"https://doi.org/10.1016/j.cell.2025.05.001","url":null,"abstract":"Mammalian organs continuously produce and consume circulating metabolites for organismal health and survival. However, the landscape of this fundamental process and its perturbation by diet and disease is unknown. Using arteriovenous metabolomics, tissue transcriptomics, and hormone arrays in multiple pathophysiological conditions in pigs, we generated an atlas of 10 cross-organ metabolite production and consumption during fasting/feeding, Western diet, and cardiovascular disease progression induced by low-density lipoprotein receptor (LDLR) deficiency. We discovered numerous instances of feeding-dependent and -independent metabolite production and consumption by organs and proposed mechanisms by which these are disrupted by Western diet via altered metabolite concentration gradients and hormones. Both Western diet and LDLR deficiency trigger the release of bile acids (BAs) by extra-hepatic organs, likely contributing to abnormally elevated circulating BA levels and consequent vascular inflammation and atherosclerosis development. These resources reveal intricate inter-organ metabolic crosstalk across pathophysiological conditions, offering biochemical insights into diet effects and cardiometabolic diseases.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"40 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145857","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

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