Cell Discovery最新文献

{"title":"Structural basis for catalytic mechanism of human phosphatidylserine synthase 1.","authors":"Yingjie Ning, Ruisheng Xu, Jie Yu, Jingpeng Ge","doi":"10.1038/s41421-025-00775-3","DOIUrl":"10.1038/s41421-025-00775-3","url":null,"abstract":"","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"20"},"PeriodicalIF":13.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566143","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":"RNA cytidine acetyltransferase NAT10 maintains T cell pathogenicity in inflammatory bowel disease.","authors":"Haixin Li, Xuemin Cai, Changfen Xu, Xinhui Yang, Xiaohan Song, Yuxin Kong, Mei Yang, Qielan Wu, Song Guo Zheng, Yiming Shao, Ping Wang, Jing Zhou, Hua-Bing Li","doi":"10.1038/s41421-025-00781-5","DOIUrl":"10.1038/s41421-025-00781-5","url":null,"abstract":"<p><p>The emerging field of epitranscriptomics is reshaping our understanding of post-transcriptional gene regulation in inflammatory diseases. N⁴-acetylcytidine (ac⁴C), the only known acetylation modification in RNA catalyzed by N-acetyltransferase 10 (NAT10), is known to enhance mRNA stability and translation, yet its role in inflammatory bowel disease (IBD) remains unclear. In this study, we discovered that Nat10 expression correlates with inflammatory and apoptotic pathways in human ulcerative colitis CD4⁺ T cells. Our further analysis revealed that the deficiency of NAT10 led to a disruption of T cell development at steady state, and identified a pivotal role for NAT10 in preserving the pathogenicity of naïve CD4⁺ T cells to induce adoptive transfer colitis. Mechanistically, the lack of NAT10 triggers the diminished stability of the anti-apoptotic gene BCL2-associated athanogene 3 (Bag3), initiating a cascade of events that includes the upregulation of apoptosis-related genes and an accelerated rate of apoptosis in T cells. Our findings reveal a previously unrecognized role of the NAT10-ac⁴C-Bag3 axis in preserving T cell balance and suggests that targeting RNA ac⁴C modification could be a promising therapeutic approach for IBD.</p>","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"19"},"PeriodicalIF":13.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555995","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":"TMEM41B is an endoplasmic reticulum Ca²⁺ release channel maintaining naive T cell quiescence and responsiveness.","authors":"Yuying Ma, Yi Wang, Xiaocui Zhao, Gang Jin, Jing Xu, Zhuoyang Li, Na Yin, Zhaobing Gao, Bingqing Xia, Min Peng","doi":"10.1038/s41421-024-00766-w","DOIUrl":"10.1038/s41421-024-00766-w","url":null,"abstract":"<p><p>In mammalian cells, endoplasmic reticulum (ER) passively releases Ca²⁺ under steady state, but channels involved remain elusive. Here, we report that TMEM41B, an ER-resident membrane protein critical for autophagy, lipid metabolism, and viral infection, functions as an ER Ca²⁺ release channel. Biochemically, purified recombinant TMEM41B forms a concentration-dependent Ca²⁺ channel in single-channel electrophysiology assays. Cellularly, TMEM41B deficiency causes ER Ca²⁺ overload, while overexpression of TMEM41B depletes ER Ca²⁺. Immunologically, ER Ca²⁺ overload leads to upregulation of IL-2 and IL-7 receptors in naive T cells, which in turn increases basal signaling of JAK-STAT, AKT-mTOR, and MAPK pathways. This dysregulation drives TMEM41B-deficient naive T cells into a metabolically activated yet immunologically naive state. ER Ca²⁺ overload also downregulates CD5, lowering the activation threshold of TMEM41B-deficient T cells and leading to heightened T cell responses during infections. In summary, we identify TMEM41B as a concentration-dependent ER Ca²⁺ release channel, revealing an unexpected role of ER Ca²⁺ in naive T cell quiescence and responsiveness.</p>","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"18"},"PeriodicalIF":13.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555996","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":"Historical loss weakens competitive behavior by remodeling ventral hippocampal dynamics.","authors":"Chuan Lai, Kai Chen, He-Zhou Huang, Xian Huang, Juan Zhang, Yu-Bo Wang, Zhiye Chen, Feng Hu, Ziyuan Guo, Heng-Ye Man, Hui-Yun Du, You-Ming Lu, Kai Shu, Dan Liu, Ling-Qiang Zhu","doi":"10.1038/s41421-024-00751-3","DOIUrl":"10.1038/s41421-024-00751-3","url":null,"abstract":"<p><p>Competitive interactions are pervasive within biological populations, where individuals engage in fierce disputes over vital resources for survival. Before the establishment of a social hierarchy within the population, this competition becomes even more intense. Historical experiences of competition significantly influence the competitive performance; individuals with a history of persistent loss are less likely to initiate attacks or win escalated contests. However, it remains unclear how historical loss directly affects the evolution of mental processes during competition and alters responses to ongoing competitive events. Here, we utilized a naturalistic food competition paradigm to track the competitive patterns of mutually unfamiliar competitors and found that a history of loss leads to reduced competitive performance. By tracking the activity of ventral hippocampal neuron ensembles, we identified clusters of neurons that responded differently to behavioral events during the competition, with their reactivity modulated by previous losses. Using a Recurrent Switch Linear Dynamical System (rSLDS), we revealed rotational dynamics in the ventral hippocampus (vHPC) during food competition, where different discrete internal states corresponded to different behavioral strategies. Moreover, historical loss modulates competitive behavior by remodeling the characteristic attributes of this rotational dynamic system. Finally, we found that an evolutionarily conserved glutamate receptor-associated protein, glutamate receptor-associated protein 1 (Grina), plays an important role in this process. By continuously monitoring the association between the attributes of the dynamic system and competitiveness, we found that restoring Grina expression effectively reversed the impact of historical loss on competitive performance. Together, our study reveals the rotational dynamics in the ventral hippocampus during competition and elucidates the underlying mechanisms through which historical loss shapes these processes.</p>","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"16"},"PeriodicalIF":13.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490904","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":"MAPK13 phosphorylates PHGDH and promotes its degradation via chaperone-mediated autophagy during liver injury.","authors":"Ru Xing, Ruilong Liu, Yongxiao Man, Chen Liu, Yajuan Zhang, Hong Gao, Weiwei Yang","doi":"10.1038/s41421-024-00758-w","DOIUrl":"10.1038/s41421-024-00758-w","url":null,"abstract":"<p><p>Drug-induced liver injury (DILI) is the leading cause of acute liver failure and poses a significant clinical challenge in both diagnosis and treatment. Serine synthesis pathway (SSP) links glycolysis to one-carbon cycle and plays an important role in cell homeostasis by regulating substance synthesis, redox homeostasis and gene expression. However, the regulatory mechanism of SSP in DILI remains unclear. Phosphoglycerate dehydrogenase (PHGDH) is the rate-limiting enzyme in SSP. Here we show that during DILI, mitogen-activated protein kinase 13 (MAPK13) is activated and then phosphorylates PHGDH at serine 371 upon oxidative stress, which triggers PHGDH protein degradation via chaperone-mediated autophagy (CMA) pathway. PHGDH degradation suppresses SSP and glutathione production, thereby exacerbating DILI and cholestatic liver injury. Importantly, both MAPK13 inhibition and dietary serine supplementation ameliorates these liver injuries. Our finding demonstrates a unique regulatory mechanism of SSP, in which MAPK13 phosphorylates PHGDH and promotes its CMA degradation, establishes its critical role in DILI and cholestatic liver injury, and highlights the therapeutic potential of MAPK13 inhibitor or dietary serine to treat these liver injuries.</p>","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"15"},"PeriodicalIF":13.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439934","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: SGF29 nuclear condensates reinforce cellular aging.","authors":"Kaowen Yan, Qianzhao Ji, Dongxin Zhao, Mingheng Li, Xiaoyan Sun, Zehua Wang, Xiaoqian Liu, Zunpeng Liu, Hongyu Li, Yingjie Ding, Si Wang, Juan Carlos Izpisua Belmonte, Jing Qu, Weiqi Zhang, Guang-Hui Liu","doi":"10.1038/s41421-025-00773-5","DOIUrl":"10.1038/s41421-025-00773-5","url":null,"abstract":"","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"17"},"PeriodicalIF":13.0,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11830007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425160","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":"Transgenerational inheritance of diabetes susceptibility in male offspring with maternal androgen exposure.","authors":"Yuqing Zhang, Shourui Hu, Shan Han, Congcong Liu, Xiaofan Liang, Yuxuan Li, Zongxuan Lin, Yiming Qin, Chunxuan Geng, Yue Liu, Linlin Cui, Jingmei Hu, Changming Zhang, Zhao Wang, Xin Liu, Jinlong Ma, Zi-Jiang Chen, Han Zhao","doi":"10.1038/s41421-025-00769-1","DOIUrl":"10.1038/s41421-025-00769-1","url":null,"abstract":"<p><p>Androgen exposure (AE) poses a profound health threat to women, yet its transgenerational impacts on male descendants remain unclear. Here, employing a large-scale mother-child cohort, we show that maternal hyperandrogenism predisposes sons to β-cell dysfunction. Male offspring mice with prenatal AE exhibited hyperglycemia and glucose intolerance across three generations, which were further exacerbated by aging and a high-fat diet. Mechanistically, compromised insulin secretion underlies this transgenerational susceptibility to diabetes. Integrated analyses of methylome and transcriptome revealed differential DNA methylation of β-cell functional genes in AE-F1 sperm, which was transmitted to AE-F2 islets and further retained in AE-F2 sperm, leading to reduced expression of genes related to insulin secretion, including Pdx1, Irs1, Ptprn2, and Cacna1c. The methylation signatures in AE-F1 sperm were corroborated in diabetic humans and the blood of sons with maternal hyperandrogenism. Moreover, caloric restriction and metformin treatments normalized hyperglycemia in AE-F1 males and blocked their inheritance to offspring by restoring the aberrant sperm DNA methylations. Our findings highlight the transgenerational inheritance of impaired glucose homeostasis in male offspring from maternal AE via DNA methylation changes, providing methylation biomarkers and therapeutic strategies to safeguard future generations' metabolic health.</p>","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"14"},"PeriodicalIF":13.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11814079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398304","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":"Human DDIT4L intron retention contributes to cognitive impairment and amyloid plaque formation.","authors":"Kai-Cheng Li, Hai-Xiang Shi, Zhen Li, Pu You, Jing Pan, Yi-Chuan Cai, Jin-Wen Li, Xue-Fei Ma, Shuo Zhang, Lei Diao, Bing Cai, Hai-Bo Wang, Liang Chen, Ying Mao, Xu Zhang","doi":"10.1038/s41421-024-00759-9","DOIUrl":"10.1038/s41421-024-00759-9","url":null,"abstract":"","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"12"},"PeriodicalIF":13.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389923","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":"NF-κB RelB suppresses the inflammatory gene expression programs of dendritic cells by competing with RelA for binding to target gene promoters.","authors":"Héctor I Navarro, Allison E Daly, Benancio Rodriguez, Sunny Wu, Kim A Ngo, Anna Fraser, Allison Schiffman, Yi Liu, Stephen T Smale, Jennifer J Chia, Alexander Hoffmann","doi":"10.1038/s41421-024-00767-9","DOIUrl":"10.1038/s41421-024-00767-9","url":null,"abstract":"<p><p>A group of autoinflammatory disorders termed relopathies arise as a consequence of NF-κB dysregulation. Genetic loss of the NF-κB subunit RelB in humans and mice leads to autoimmunity and lethal multi-organ inflammatory pathology. Our recent study showed that this inflammatory pathology is independent of type I interferon signaling, and further identified dysregulation of a set of pro-inflammatory NF-κB target genes. However, it remains unknown how the loss of RelB leads to the dysregulation of these NF-κB motif-containing pro-inflammatory genes. Here, we report epigenome profiling studies revealing that RelB is associated with pro-inflammatory genes in dendritic cells. While these genes recruit RelA binding upon exposure to a maturation stimulus, we observed substantially more RelA recruitment in the absence of RelB. For these genes, we found that elevated RelA recruitment is correlated with elevated gene expression. To test whether RelB may compete with RelA for binding to NF-κB-regulated gene promoters via competition for κB sites, we generated a new mouse strain (RelB^DB/DB) that harbors targeted point mutations in the RelB DNA binding domain that eliminates high-affinity DNA binding. We found that this targeted mutation in the RelB DNA binding domain is sufficient to drive multi-organ inflammatory pathology. These results provide insights into the biological mechanism of RelB as a suppressor of pro-inflammatory gene expression and autoimmune pathology.</p>","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"13"},"PeriodicalIF":13.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389931","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 tumor-secreted protein utilizes glucagon release to cause host wasting.","authors":"Guangming Ding, Yingge Li, Chen Cheng, Kai Tan, Yifei Deng, Huiwen Pang, Zhongyuan Wang, Peixuan Dang, Xing Wu, Elisabeth Rushworth, Yufeng Yuan, Zhiyong Yang, Wei Song","doi":"10.1038/s41421-024-00762-0","DOIUrl":"10.1038/s41421-024-00762-0","url":null,"abstract":"<p><p>Tumor‒host interaction plays a critical role in malignant tumor-induced organ wasting across multiple species. Despite known regulation of regional wasting of individual peripheral organs by tumors, whether and how tumors utilize critical host catabolic hormone(s) to simultaneously induce systemic host wasting, is largely unknown. Using the conserved yki^3SA-tumor model in Drosophila, we discovered that tumors increase the production of adipokinetic hormone (Akh), a glucagon-like catabolic hormone, to cause systemic host wasting, including muscle dysfunction, lipid loss, hyperglycemia, and ovary atrophy. We next integrated RNAi screening and Gal4-LexA dual expression system to show that yki^3SA-gut tumors secrete Pvf1 to remotely activate its receptor Pvr in Akh-producing cells (APCs), ultimately promoting Akh production. The underlying molecular mechanisms involved the Pvf1-Pvr axis that triggers Mmp2-dependent ECM remodeling of APCs and enhances innervation from the excitatory cholinergic neurons. Interestingly, we also confirmed the similar mechanisms governing tumor-induced glucagon release and organ wasting in mammals. Blockade of either glucagon or PDGFR (homolog of Pvr) action efficiently ameliorated organ wasting in the presence of malignant tumors. Therefore, our results demonstrate that tumors remotely promote neural-associated Akh/glucagon production via Pvf1-Pvr axis to cause systemic host wasting.</p>","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"11 1","pages":"11"},"PeriodicalIF":13.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381701","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}