Cell Discovery最新文献

{"title":"Lineage tracing reveals the origins and dynamics of macrophages in lung injury and repair.","authors":"Hengwei Jin, Jialing Mou, Huan Zhu, Kuo Liu, Mingjun Zhang, Zhenqian Zhang, Stefan Pflanz, Karim Ei Kasmi, Zhaoyuan Liu, Florent Ginhoux, Kathy O Lui, Bin Zhou","doi":"10.1038/s41421-025-00859-0","DOIUrl":"10.1038/s41421-025-00859-0","url":null,"abstract":"<p><p>Macrophages play a vital role in tissue repair and regeneration following injury. However, the cell fate, dynamic responses, and functions of macrophages from various origins during lung injury and repair are not fully understood. Here, we used genetic lineage tracing and scRNA-seq approaches to explore the temporal and spatial roles of tissue-resident and infiltrating macrophages during pulmonary fibrosis. We observed a sharp reduction in tissue-resident macrophages during the early inflammatory phase, with their numbers stabilizing during recovery. Monocytes contributed substantially to the macrophage population during the fibrotic phase, initially differentiating into interstitial macrophages and later transitioning into alveolar macrophages through a transient state. Genetic ablation of monocytes led to a reduction in the number of infiltrating macrophages and alleviated pulmonary fibrosis. Mechanistically, Notch signaling was negatively correlated with Wnt/β-catenin signaling in the regulation of monocyte recruitment and pulmonary fibrosis. Our study reveals the dynamic contributions and functions of macrophages from various sources in lung injury and regeneration.</p>","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"12 1","pages":"3"},"PeriodicalIF":12.5,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12804754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145970591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prefrontal cortex-to-hypothalamic outputs orchestrate cue-potentiated palatable food consumption via AMPKβ2 signaling.","authors":"Jiakun Xiang, Minghong Shi, Jiajia Kang, Xingyuan Zhang, Jiankai Ling, Wei Zhan, Dianyi Li, Rongfeng K Hu, Zhi-Xiang Xu","doi":"10.1038/s41421-025-00857-2","DOIUrl":"10.1038/s41421-025-00857-2","url":null,"abstract":"<p><p>Cognitive factors critically influence appetite and food consumption, contributing to the increasing incidence of obesity in modern obesogenic environments. However, the cellular and molecular mechanisms underlying this phenomenon remain poorly understood. Here, using calcium imaging in freely moving mice, we found that neurons in the prelimbic cortex (PrL) underwent activity-dependent plasticity in response to learned environmental cues paired with a high-fat diet (HFD). The activity of these neurons reliably predicted the duration of food consumption. Transcriptomic analyses further revealed significant alterations in ATP metabolic processes in the PrL following HFD-associated learning. Notably, the depletion of AMPKβ2, a subunit of AMPK that senses ATP dynamics, abolished PrL plasticity during HFD associative learning and prevented the cue-driven overconsumption of palatable food. At the circuitry level, the activity of PrL^CaMKIIα+ neuronal projections to orexin neurons in the lateral hypothalamus was required for HFD overconsumption under conditioned contexts. Collectively, our findings elucidate a cellular and molecular framework in a cortical-hypothalamic pathway that regulates cue-evoked HFD overconsumption, highlighting AMPKβ2 as a promising therapeutic target for treating eating disorders.</p>","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"12 1","pages":"2"},"PeriodicalIF":12.5,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12775431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145910529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"tRNA m¹A modification is essential for gut homeostasis and function of group 3 innate lymphoid cells.","authors":"Jingyu Li, Zirun Tang, Yunzhu Chen, Xuemin Cai, Longyan Wu, Gaoyang Wang, Chen Kan, Bin Li, Bing Su, Huabin Li, Coco Chu, Hua-Bing Li","doi":"10.1038/s41421-025-00850-9","DOIUrl":"10.1038/s41421-025-00850-9","url":null,"abstract":"<p><p>Group 3 innate lymphoid cells (ILC3s) play crucial roles in maintaining intestinal homeostasis and defending against bacterial infections. However, the epigenetic mechanisms that regulate ILC3 responses are not well understood. In this study, we show that Trmt61a, the methyltransferase responsible for the m¹A58 tRNA modification, is predominantly expressed in ILC3s. We found that specific depletion of TRMT61A in ILC3s leads to dysregulated cell cycle and a reduction in cell numbers. Notably, mice with an ILC3-specific TRMT61A deficiency exhibit dysbiosis, but antibiotic treatment can restore colonic ILC3 levels. Furthermore, these mice exhibit increased susceptibility to experimental intestinal inflammation and enteric bacterial infection. Our findings uncover a previously unrecognized role for TRMT61A mediated m¹A modification in the regulation of intestinal ILC3s, essential for protecting intestinal tissue during inflammation and enhancing innate immunity against enteric pathogens.</p>","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"12 1","pages":"1"},"PeriodicalIF":12.5,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12764812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145896100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Luminal hormone-responsive cells tune the regenerative remodeling of mammary glands in large mammals.","authors":"Yongtao Li, Liping Zhang, Tao Luo, Wenying Zhang, Teng Wang, Fanming Liu, Shengda Lin, Jun Luo, Jianxin Liu, Jinrong Peng, Chaochen Wang, Wei Wang, Hengbo Shi","doi":"10.1038/s41421-025-00848-3","DOIUrl":"10.1038/s41421-025-00848-3","url":null,"abstract":"<p><p>The remodeling of mammary glands during pregnancy is essential for initiating lactation. In dairy animals, the overlap of pregnancy and mammary involution triggers a unique process, regenerative remodeling, which is critical for extending lactation duration and enhancing milk production. Unlike the complete regression of lobuloalveolar structures during involution, the regenerative remodeling preserves alveolar structures and promotes rapid mammary gland renewal. However, the cellular and molecular mechanisms underlying such process remain elusive. Here, taking dairy goats (Capra hircus) as a ruminant model, we identified four luminal cell populations through single-cell RNA-sequencing and found a significant reduction in luminal hormone-responsive (LumHR) cells and an increase in luminal secretory precursors (LumSecP) during regenerative remodeling. A reduction of LumHR cells during regenerative remodeling is essential for promoting the accumulation of LumSecP. Goat mammary organoids and in vivo genetic ablation assays suggested that LumHR cells function as a crucial switch for the differentiation of LumSecP to LumSec cells through the prolactin receptor pathway. Furthermore, high levels of IRF1 inhibited while downregulation of IRF1 stimulated the proliferation of LumHR cells. We showed that IRF1 regulated the dynamics of LumHR cells through hormonal signaling targets, including ESRRB. Our findings identified a key cell type responsible for the dynamics of luminal lineages during regenerative remodeling in large mammals and highlighted the potential for accelerating tissue regeneration through targeted modulation of lineage stage-specific regulators.</p>","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"105"},"PeriodicalIF":12.5,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12749961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145854498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Robust generation of clinically applicable human pluripotent stem cells from peripheral blood by chemical reprogramming.","authors":"Xiaodi Fu, Fangqi Peng, Ruyi Cai, Jingping Mao, Tianxing Liu, Yingshuai Dong, Ruoqi Cheng, Zhihan Yang, Guanxian Chen, Cheng Li, Rong Mu, Lin Cheng, Yanglu Wang, Jingyang Guan, Hongkui Deng","doi":"10.1038/s41421-025-00852-7","DOIUrl":"10.1038/s41421-025-00852-7","url":null,"abstract":"","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"103"},"PeriodicalIF":12.5,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12727690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145818160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal acute SARS-CoV-2 infection impairs preimplantation embryo development and reprograms the early offspring hematopoietic system.","authors":"Meiling Zhang, Di Liu, Songmao Li, Jiansheng Liu, Fanghao Guo, Haibin Zhu, Li Zhang, Di Sun, Yu Yan, Yanquan Li, Rui Qiao, Haixia Ding, Qing Zhang, Mengxi Guo, Yongjian Ma, Zhiwei Liu, Wen Li, Yuxuan Zheng","doi":"10.1038/s41421-025-00856-3","DOIUrl":"10.1038/s41421-025-00856-3","url":null,"abstract":"<p><p>SARS-CoV-2 infection has raised significant concerns regarding its impact on assisted reproductive technology. We found that oocyte retrieval during acute SARS-CoV-2 infection significantly reduced the rates of good-quality blastocyst formation, but the underlying molecular mechanisms remain poorly understood. To address this, we investigated the effects of maternal acute SARS-CoV-2 infection on preimplantation embryo development and the early offspring hematopoietic system. Using single-cell RNA sequencing (scRNA-seq), we identified developmental delays in morphologically normal blastocysts from infected mothers, characterized by prolonged expression of zygotic genome activation-related genes, downregulation of mTORC1 signaling, and altered energy metabolism, including suppressed oxidative phosphorylation (OXPHOS) and enhanced glycolysis. We further revealed that maternal acute infection induced abnormal methylation/demethylation patterns in preimplantation embryos. To assess the potential long-term impact on offspring, we conducted integrated multi-tissue analyses, including bulk RNA-seq and genome-wide DNA methylation profiling of placental tissues, along with scRNA-seq of umbilical cord blood (UCB) cells from neonates delivered by SARS-CoV-2-infected mothers. Neonates exhibited elevated levels of inflammatory cytokines and an increased abundance of monocytes, indicating an activated myelopoiesis response. In addition, hematopoietic stem and progenitor cells (HSPCs) from UCB showed reduced OXPHOS activity and a skewed differentiation bias toward the myeloid lineage, potentially impacting long-term immune function. Collectively, these findings reveal that maternal acute SARS-CoV-2 infection impairs preimplantation embryo development and leaves a lasting imprint on offspring hematopoietic health through dysregulated energy metabolism, epigenetic modifications, and altered immune responses.</p>","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"104"},"PeriodicalIF":12.5,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12728194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145818169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ncBAF recognizes the nucleosome through BCL7A in chromatin remodeling.","authors":"Kangjing Chen, Liwen Du, Yumin Liu, Mo Chen, Zhucheng Chen","doi":"10.1038/s41421-025-00858-1","DOIUrl":"10.1038/s41421-025-00858-1","url":null,"abstract":"","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"102"},"PeriodicalIF":12.5,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12708618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145767187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A receptor-like kinase recognizes viral proteins at the trans-Golgi network/early endosome and inhibits infection in rice.","authors":"Huacai Wang, Yawen Liu, Mengting Zhang, Rongxiang Fang, Yongsheng Yan","doi":"10.1038/s41421-025-00847-4","DOIUrl":"10.1038/s41421-025-00847-4","url":null,"abstract":"<p><p>Receptor-like kinases (RLKs) reside on the cell surface and recognize apoplastic colonization by plant-infecting microbes to initiate immune responses. Whether RLKs can also recognize intracellular colonization by viruses to activate antiviral defense mechanisms in plants remains unknown. Here, we report the identification and characterization of a trans-Golgi network/early endosome (TGN/EE)-localized RLK that recognizes viral proteins and inhibits infection in rice. OsVIRK1, a cysteine-rich receptor-like kinase, promotes rice resistance to rice stripe virus (RSV), one of the most devastating viruses of rice. OsVIRK1 transcription is induced in RSV-infected rice, and its protein accumulates through autophosphorylation and redox-mediated regulation. OsVIRK1 physically interacts with the RSV coat protein (CP), a known immune elicitor, and nonstructural protein 3 (NS3), an antiviral RNA-silencing suppressor, at the TGN/EE. OsVIRK1 is required for CP-triggered defense gene expression. It phosphorylates NS3, reducing NS3 accumulation in the cytoplasm and thus repressing its activity as an RNA-silencing suppressor. Our findings suggest that OsVIRK1 recognizes viral proteins at the TGN/EE to inhibit infection by activating plant antiviral immunity and dampening viral counterdefense.</p>","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"101"},"PeriodicalIF":12.5,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12708648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145767197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author Correction: Treatment of liver cirrhosis using hepatocyte-derived liver progenitor-like cells: a prospective, open-label, single-arm, safety trial.","authors":"Kang He, Xue-Jing Zhu, Yao-Ping Shi, Wei-Jian Huang, Tai-Hua Yang, Zhi-Feng Xi, Qi-Gen Li, Han-Yong Sun, Li-Jun Qian, Xiao-Song Chen, Pei-Ying Li, Xu Zhou, Gui-Ying Gu, Fan Li, Wen-Ming Liu, Cai-Yang Chen, Jie Zhao, Hong-Ping Wu, Fang-Rong Yan, Michael Ott, Amar Deep Sharma, Hui Liu, Wei-Feng Yu, Bo Zhai, He-Xin Yan, Qiang Xia","doi":"10.1038/s41421-025-00862-5","DOIUrl":"10.1038/s41421-025-00862-5","url":null,"abstract":"","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"99"},"PeriodicalIF":12.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12695932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145721152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural and mechanistic insights into the herpes simplex virus type 1 helicase-primase primosome.","authors":"Yaqi Wu, Ziyi Jiang, Xiaoling Chen, Danyang Li, Zhengyu Zhang, Changjiang Dong","doi":"10.1038/s41421-025-00855-4","DOIUrl":"10.1038/s41421-025-00855-4","url":null,"abstract":"<p><p>DNA unwinding and primer synthesis are fundamental processes in genome replication. The human herpes simplex virus type 1 (HSV-1) helicase-primase forms a unique heterotrimeric primosome that is essential for viral DNA unwinding and primer synthesis and represents an ideal drug target. However, its molecular mechanism remains poorly understood. Here we report the cryo-electron microscopic structure of the primosome in complex with single-stranded DNA, ADP and Mg²⁺ to 3.47 Å resolution, which reveals that the primosome forms an unprecedented architecture in a fully open DNA binding groove between the helicase domains 1A and 2A-2B and that the primase subunit UL52 interacts extensively with the helicase subunit UL5 and accessory protein subunit UL8. Integrating mutagenesis, biochemical assays, structural analysis and 3D variability display analysis, we have identified the active sites of the ATPase, helicase and primase and critical interfaces between UL52, UL5 and UL8. Our work suggests that the primosome unwinds and translocates DNA via bidirectional rotation, and proposes a mechanistic model for DNA-dependent ATPase activation and alternating activity between helicase and primase. Herpesviridae family viruses pose significant threats to human health worldwide, and this trimeric assembly of primosomes is conserved. Our work provides a framework for understanding replication mechanisms across related viruses and for the rational design of broad-spectrum antivirals.</p>","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"100"},"PeriodicalIF":12.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12695949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145721130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}