IF 64.5 1区生物学

Cell Pub Date : 2025-06-09 DOI: 10.1016/j.cell.2025.05.012

William Kong, Wan-Jin Lu, Megha Dubey, Rahul K. Suryawanshi, Sivakamasundari Vijayakumar, Youngtae Jeong, Saurabh Gombar, Maximilian Diehn, Kunyoo Shin, Melanie Ott, Yueh-hsiu Chien, Kavita Y. Sarin, Tushar J. Desai, Philip A. Beachy

{"title":"Neuroendocrine cells orchestrate regeneration through Desert hedgehog signaling","authors":"William Kong, Wan-Jin Lu, Megha Dubey, Rahul K. Suryawanshi, Sivakamasundari Vijayakumar, Youngtae Jeong, Saurabh Gombar, Maximilian Diehn, Kunyoo Shin, Melanie Ott, Yueh-hsiu Chien, Kavita Y. Sarin, Tushar J. Desai, Philip A. Beachy","doi":"10.1016/j.cell.2025.05.012","DOIUrl":"https://doi.org/10.1016/j.cell.2025.05.012","url":null,"abstract":"Understanding the mechanisms underlying mammalian regeneration may enable development of novel regenerative therapies. We present a mechanism wherein Desert hedgehog (Dhh), secreted from epithelial neuroendocrine cells, elicits a regenerative/protective response from mesenchymal cells. In mammalian airway, this mesenchymal response strikingly amplifies the initial signal from rare neuroendocrine cells to activate the entire tissue for survival and regeneration upon injury from SO2 gas inhalation or following influenza or SARS-CoV-2 infection. Similar epithelial-mesenchymal feedback (EMF) signaling directed by Dhh from neuroendocrine β cells likewise protects mouse pancreatic islets from streptozotocin (STZ) injury. A role for EMF signaling in human pancreatic islets is suggested by higher incidence of diabetes in patients treated with Hedgehog pathway inhibitors. Remarkably, EMF augmentation by small-molecule Hedgehog pathway agonism protects against STZ injury of pancreatic β cells and shields against airway injury from SO2 and influenza infection, with potential protective/therapeutic utility in chemical or infectious airway injury and in diabetes.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"522 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144237998","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

Microbiota-derived inosine programs protective CD8+ T cell responses against influenza in newborns 微生物来源的肌苷程序保护CD8+ T细胞对新生儿流感的反应

IF 64.5 1区生物学

Cell Pub Date : 2025-06-09 DOI: 10.1016/j.cell.2025.05.013

Joseph Stevens, Erica Culberson, Jeremy Kinder, Alicia Ramiriqui, Jerilyn Gray, Madeline Bonfield, Tzu-Yu Shao, Faris Al Gharaibeh, Laura Peterson, Shelby Steinmeyer, Emily M. Eshleman, Shikha Negi, William Zacharias, Gloria Pryhuber, Oindrila Paul, Shaon Sengupta, Theresa Alenghat, Sing Sing Way, Hitesh Deshmukh

{"title":"Microbiota-derived inosine programs protective CD8+ T cell responses against influenza in newborns","authors":"Joseph Stevens, Erica Culberson, Jeremy Kinder, Alicia Ramiriqui, Jerilyn Gray, Madeline Bonfield, Tzu-Yu Shao, Faris Al Gharaibeh, Laura Peterson, Shelby Steinmeyer, Emily M. Eshleman, Shikha Negi, William Zacharias, Gloria Pryhuber, Oindrila Paul, Shaon Sengupta, Theresa Alenghat, Sing Sing Way, Hitesh Deshmukh","doi":"10.1016/j.cell.2025.05.013","DOIUrl":"https://doi.org/10.1016/j.cell.2025.05.013","url":null,"abstract":"Early-life susceptibility to respiratory viral infections remains a major public health concern, yet the underlying mechanisms are poorly understood. We demonstrate that antibiotic-induced dysbiosis impairs influenza-specific CD8+ T cell immunity in infant mice and humans through the disruption of nuclear factor interleukin 3 (NFIL3)-dependent T cell programming. Mechanistically, we show that dysbiosis reduces intestinal and circulating inosine levels, disrupting NFIL3’s epigenetic regulation of T cell factor 1 (TCF1) expression. This leads to intrinsic defects in CD8+ T cell proliferation and differentiation, diminished effector responses, and impaired formation of tissue-resident memory cells. Bifidobacterium colonization restores intestinal and pulmonary inosine levels, establishing a specific pathway of gut-lung metabolic communication. Notably, inosine supplementation rescues NFIL3-dependent regulation of TCF1, enhancing CD8+ T cell responses and protection against influenza infection in dysbiotic infants. Our findings reveal how early-life microbial communities shape antiviral immunity and identify inosine as a therapeutic target for enhancing respiratory defenses in infants.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"9 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144237996","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

Sensory Neurons that Detect Stretch and Nutrients in the Digestive System 在消化系统中检测拉伸和营养的感觉神经元

IF 64.5 1区生物学

Cell Pub Date : 2025-06-07 DOI: 10.1016/j.cell.2025.05.043

Erika K. Williams, Rui B. Chang, David E. Strochlic, Benjamin D. Umans, Bradford B. Lowell, Stephen D. Liberles

引用次数: 0

Microbiome mismatches from microbiota transplants lead to persistent off-target metabolic and immunomodulatory effects 来自微生物群移植的微生物组不匹配导致持续的脱靶代谢和免疫调节效应

IF 64.5 1区生物学

Cell Pub Date : 2025-06-06 DOI: 10.1016/j.cell.2025.05.014

Orlando DeLeon, Mora Mocanu, Alan Tan, Ashley M. Sidebottom, Jason Koval, Hugo D. Ceccato, Sarah Kralicek, John J. Colgan, Marissa M. St. George, Joash M. Lake, Michael Cooper, Jingwen Xu, Julia Moore, Qi Su, Zhilu Xu, Siew C. Ng, Francis K.L. Chan, Hein M. Tun, Candace M. Cham, Cambrian Y. Liu, Eugene B. Chang

{"title":"Microbiome mismatches from microbiota transplants lead to persistent off-target metabolic and immunomodulatory effects","authors":"Orlando DeLeon, Mora Mocanu, Alan Tan, Ashley M. Sidebottom, Jason Koval, Hugo D. Ceccato, Sarah Kralicek, John J. Colgan, Marissa M. St. George, Joash M. Lake, Michael Cooper, Jingwen Xu, Julia Moore, Qi Su, Zhilu Xu, Siew C. Ng, Francis K.L. Chan, Hein M. Tun, Candace M. Cham, Cambrian Y. Liu, Eugene B. Chang","doi":"10.1016/j.cell.2025.05.014","DOIUrl":"https://doi.org/10.1016/j.cell.2025.05.014","url":null,"abstract":"Fecal microbiota transplant (FMT) is an increasingly used intervention, but its suitability to restore regional gut microbiota, particularly in the small bowel (SB), must be questioned because of its predominant anaerobic composition. In human subjects receiving FMT by upper endoscopy, duodenal engraftment of anaerobes was observed after 4 weeks. We hypothesized that peroral FMTs create host-microbe mismatches that impact SB homeostasis. To test this, antibiotic-treated specific-pathogen-free (SPF) mice were given jejunal, cecal, or fecal microbiota transplants (JMTs, CMTs, or FMTs, respectively) and studied 1 or 3 months later. JMT and FMT altered regional microbiota membership and function, energy balance, and intestinal and hepatic transcriptomes; JMT favored host metabolic pathways and FMT favored immune pathways. MTs drove regional intestinal identity (Gata4, Gata6, and Satb2) and downstream differentiation markers. RNA sequencing (RNA-seq) of metabolite-exposed human enteroids and duodenal biopsies post-FMT confirmed transcriptional changes in mice. Thus, regional microbial mismatches after FMTs can lead to unintended consequences and require rethinking of microbiome-based interventions.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"62 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144228851","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

Infrequent strong connections constrain connectomic predictions of neuronal function 不频繁的强连接限制了神经元功能的连接组预测

IF 64.5 1区生物学

Cell Pub Date : 2025-06-02 DOI: 10.1016/j.cell.2025.05.007

Timothy A. Currier, Thomas R. Clandinin

引用次数: 0

Centromeric DNA amplification triggered by viral proteins activates nuclear cGAS 由病毒蛋白触发的着丝粒DNA扩增激活核cGAS

IF 64.5 1区生物学

Cell Pub Date : 2025-06-02 DOI: 10.1016/j.cell.2025.05.008

Xavier Lahaye, Patrick Tran Van, Camellia Chakraborty, Anna Shmakova, Ngoc Tran Bich Cao, Hermine Ferran, Ouardia Ait-Mohamed, Mathieu Maurin, Joshua J. Waterfall, Benedikt B. Kaufer, Patrick Fischer, Thomas Hennig, Lars Dölken, Patrick Lomonte, Daniele Fachinetti, Nicolas Manel

{"title":"Centromeric DNA amplification triggered by viral proteins activates nuclear cGAS","authors":"Xavier Lahaye, Patrick Tran Van, Camellia Chakraborty, Anna Shmakova, Ngoc Tran Bich Cao, Hermine Ferran, Ouardia Ait-Mohamed, Mathieu Maurin, Joshua J. Waterfall, Benedikt B. Kaufer, Patrick Fischer, Thomas Hennig, Lars Dölken, Patrick Lomonte, Daniele Fachinetti, Nicolas Manel","doi":"10.1016/j.cell.2025.05.008","DOIUrl":"https://doi.org/10.1016/j.cell.2025.05.008","url":null,"abstract":"The cGAS-cGAMP-STING pathway is crucial for antiviral immunity. While cytosolic cGAS detects viral DNA, most DNA viruses shield their genome and invade the nucleus, where chromatin restricts cGAS activation. How viruses may activate nuclear cGAS is not well understood. Here, we show that several herpesvirus proteins trigger nuclear cGAS activation by perturbing centromeres, where cGAS is enriched. The herpes simplex virus type 1 (HSV-1) ubiquitin ligase infected cell protein 0 (ICP0), which degrades centromeric proteins, promotes centromeric DNA amplification through the translesion DNA synthesis (TLS) pathway in quiescent monocyte-derived cells, thereby activating nuclear cGAS. During infection, HSV-1 evades this detection by also expressing UL36USP, a suppressor of TLS. Similarly to ICP0, the cytomegalovirus IE1 protein causes centromeric DNA amplification and cGAS activation. We define this mechanism as viral-induced centromeric DNA amplification and recognition (VICAR), uncovering a non-mitotic, immune-activating role of centromeres.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"37 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192783","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

Transcription factor condensates: Preventing aggregation by DNA binding 转录因子凝聚物：通过DNA结合防止聚集

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

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