Cell reports最新文献

RUNX1-ETO oncoprotein levels determine the balance between endothelial reprogramming and pre-leukemic growth in a human ES cell model of AML. RUNX1-ETO癌蛋白水平决定了AML人ES细胞模型中内皮重编程和白血病前期生长之间的平衡。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-19 DOI: 10.1016/j.celrep.2026.118157

Katerina Terolli, Floyd Hassenrueck, Alexander Maytum, Peter Keane, Lea Flippe, Sophie G Kellaway, Merel van der Meulen, Olaf T Heidenreich, Edouard G Stanley, Elizabeth S Ng, Andrew G Elefanty, Constanze Bonifer

{"title":"RUNX1-ETO oncoprotein levels determine the balance between endothelial reprogramming and pre-leukemic growth in a human ES cell model of AML.","authors":"Katerina Terolli, Floyd Hassenrueck, Alexander Maytum, Peter Keane, Lea Flippe, Sophie G Kellaway, Merel van der Meulen, Olaf T Heidenreich, Edouard G Stanley, Elizabeth S Ng, Andrew G Elefanty, Constanze Bonifer","doi":"10.1016/j.celrep.2026.118157","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118157","url":null,"abstract":"In t(8;21) acute myeloid leukemia (AML), the RUNX1 DNA binding domain is fused to RUNX1T1 (ETO) producing the RUNX1-ETO fusion protein. We previously showed that t(8;21) leukemic stem cells aberrantly activate endothelial signaling pathways to initiate blast cell proliferation. Here, we employed a human embryonic stem cell (ESC) line carrying an inducible RUNX1-ETO transgene to determine whether endothelial signaling pathway activation depends on disease progression or is directly induced by RUNX1-ETO. Single-cell analyses demonstrate that RUNX1-ETO reprograms ESC-derived myeloid progenitors towards endothelial cells. We show (1) that endothelial reprogramming is RUNX1-ETO concentration-dependent and irreversible, (2) at similar RUNX1-ETO and RUNX1 expression levels, a sub-population of blood progenitors can escape reprogramming, and (3) keeps proliferating when co-cultured with endothelial cells. Our experiments highlight the role of cellular interactions in the maintenance of pre-leukemic cells and provide important insights into the earliest stages of genomic reprogramming by oncogenic transcription factors.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118157"},"PeriodicalIF":7.7,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223428","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 conserved NUS-1/DHDDS-1 complex links N-glycosylation to lipid and lysosomal homeostasis in C. elegans. 保守的NUS-1/DHDDS-1复合体将n -糖基化与线虫的脂质和溶酶体稳态联系起来。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-19 DOI: 10.1016/j.celrep.2026.118178

Meixi Gong, Wentao Zhao, Yilin Du, Lingfan Zhu, Yile Zhai, Yuxiao Xie, Chen Liu, Wenfei Li, Pei Zhao, Zhe Zhang

{"title":"The conserved NUS-1/DHDDS-1 complex links N-glycosylation to lipid and lysosomal homeostasis in C. elegans.","authors":"Meixi Gong, Wentao Zhao, Yilin Du, Lingfan Zhu, Yile Zhai, Yuxiao Xie, Chen Liu, Wenfei Li, Pei Zhao, Zhe Zhang","doi":"10.1016/j.celrep.2026.118178","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118178","url":null,"abstract":"N-glycosylation is essential for proteome integrity, yet the systemic roles of the cis-prenyltransferase (cis-PT) complex remain poorly defined. Using Caenorhabditis elegans, we demonstrate that this complex is a dual regulator of global lipid and lysosomal homeostasis. Mechanistically, NUS-1 physically associates with the core oligosaccharyltransferase (OST) complex to coordinate N-glycan transfer. Loss of NUS-1/DHDDS-1 triggers endoplasmic reticulum stress, lysosomal collapse, and systemic lipopenia. This lipid defect arises from impaired N-glycosylation of the SREBP cleavage-activating protein (SCAP). cis-PT deficiency causes unglycosylated SCAP to undergo massive degradation and absolute physical entrapment within the ER, preventing SREBP nuclear translocation and downstream lipid synthesis. Furthermore, pathogenic mutations cause dysfunction through distinct molecular mechanisms: pocket integrity disruption or catalytic impairment. These findings uncover an essential crosstalk between protein glycosylation and global lipid metabolism, providing a mechanistic framework for understanding the systemic pathophysiology of congenital disorders of glycosylation (CDG).","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 11","pages":"118178"},"PeriodicalIF":7.7,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223436","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

Sequential TPRX1 and HERVL activation delineates a progression toward the totipotent-like state. 顺序的TPRX1和HERVL激活描述了向全能样状态的进展。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-17 DOI: 10.1016/j.celrep.2026.118163

An Huang, Nan Jiang, Sen Luo, Xi Kong, Simeng Yi, Shigang Yin, Jianhua Peng, Yong Jiang, Huangfan Xie, Bingqing Xie

{"title":"Sequential TPRX1 and HERVL activation delineates a progression toward the totipotent-like state.","authors":"An Huang, Nan Jiang, Sen Luo, Xi Kong, Simeng Yi, Shigang Yin, Jianhua Peng, Yong Jiang, Huangfan Xie, Bingqing Xie","doi":"10.1016/j.celrep.2026.118163","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118163","url":null,"abstract":"The in vitro induction of 8-cell-like cells (8CLCs) from human pluripotent stem cells (hPSCs) provides a model to study the regulatory principles of totipotency and zygotic genome activation (ZGA). However, the cellular dynamics underlying 8CLC emergence remain poorly understood. Here, we generate a TPRX1-EGFP/HERVL-tdTomato dual-reporter hPSC line to resolve the stepwise acquisition of totipotent-like identity. We show that 8CLC induction follows an ordered trajectory in which TPRX1 activation precedes the emergence of TPRX1+HERVL+ cells, which most closely resemble the in vivo 8-cell embryo transcriptionally. Single-cell transcriptomics and time-resolved flow cytometry further define a continuous transition from the primed state through a TPRX1+ intermediate to the HERVL+ 8CLC state. CRISPRi and RNA-directed perturbations support functional contributions of HERVL elements and HERVL-derived RNA to this transition, while potential locus-dependent mechanisms remain unresolved. Together, these findings establish sequential TPRX1 and HERVL activation as a defining feature of human 8CLC induction.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 11","pages":"118163"},"PeriodicalIF":7.7,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149219849","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

Molecular triage and isoform protection safeguard ubiquitin chain editing on DNA. 分子分类和异构体保护保障DNA上的泛素链编辑。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-16 DOI: 10.1016/j.celrep.2026.118137

Xianzhen Zhou, Martin Attwood, Alexandra McStea, Benjamin Foster, Ian Gibbs-Seymour

引用次数: 0

The COX2-PGE₂-PKA axis suppresses antiviral immunity by inhibiting mtDNA-dependent STING activation. COX2-PGE2-PKA轴通过抑制mtdna依赖性STING激活来抑制抗病毒免疫。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-16 DOI: 10.1016/j.celrep.2026.118154

Pham Thuy Tien Vo, Julien Cicero, Zichen Wang, Hiroyuki Hakozaki, Thomas S Hoang, Sendi Rafael Adame-Garcia, Dana J Ramms, Kuniaki Sato, Erica Stevenson, Yuan Zhou, Katie Fan, Juliette A Bokor, Vasiliya Kril, Cara Schiavon, Scott B Biering, Danielle L Swaney, Nevan J Krogan, Johannes Schöneberg, Uri Manor, J Silvio Gutkind

{"title":"The COX2-PGE2-PKA axis suppresses antiviral immunity by inhibiting mtDNA-dependent STING activation.","authors":"Pham Thuy Tien Vo, Julien Cicero, Zichen Wang, Hiroyuki Hakozaki, Thomas S Hoang, Sendi Rafael Adame-Garcia, Dana J Ramms, Kuniaki Sato, Erica Stevenson, Yuan Zhou, Katie Fan, Juliette A Bokor, Vasiliya Kril, Cara Schiavon, Scott B Biering, Danielle L Swaney, Nevan J Krogan, Johannes Schöneberg, Uri Manor, J Silvio Gutkind","doi":"10.1016/j.celrep.2026.118154","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118154","url":null,"abstract":"The stimulator of interferon genes (STING) pathway is essential for mounting robust innate immunity, yet its chronic activation can drive detrimental inflammation. Although multiple cell-autonomous mechanisms that restrain STING signaling have been reported, whether inflammatory mediators within the tissue microenvironment regulate STING activation remains elusive. Using herpes simplex virus type 1 infection as a model of STING activation, we revealed that the COX2-PGE2-PKA axis functions as a critical negative regulator of STING-mediated antiviral innate immunity. Mechanistically, PGE2 acts through the EP4-PKA cascade to induce PTEN-induced kinase 1 (PINK1)-mediated mitophagy by phosphorylating STOML2 at Ser29. This pathway facilitates the clearance of damaged mitochondria that serve as a source of immunostimulatory cytosolic mitochondrial DNA, thereby attenuating downstream STING activation and type I interferons while promoting viral replication. Together, these findings establish mitochondrial quality control as the mechanistic link between PGE2 signaling and mtDNA-dependent STING activation and identify the COX2-PGE2-PKA pathway as a druggable therapeutic target to enhance STING-mediated innate immunity.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118154"},"PeriodicalIF":7.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206580","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-species atlas of bacterial RNA 3' ends reveals termination mechanistic signatures and evolutionary patterns. 细菌RNA 3′末端的跨物种图谱揭示了终止机制特征和进化模式。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-16 DOI: 10.1016/j.celrep.2026.118076

Amir Bar, Yael Altuvia, Michal Eldar, Hanah Margalit

{"title":"Cross-species atlas of bacterial RNA 3' ends reveals termination mechanistic signatures and evolutionary patterns.","authors":"Amir Bar, Yael Altuvia, Michal Eldar, Hanah Margalit","doi":"10.1016/j.celrep.2026.118076","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118076","url":null,"abstract":"Deciphering the generation mechanisms and regulatory roles of bacterial transcript 3' termini requires large-scale 3' terminus data. We repurpose PATHOgenex, an available RNAtag-seq dataset, leveraging RNAtag-seq-specific read patterns associated with 3' termini to generate the \"Bacterminome\" atlas, a rich resource of species- and condition-dependent transcript 3' termini of 32 bacterial human pathogens grown under 10-12 conditions. Analysis of sequence elements near 3' termini revealed, along with the classical intrinsic terminator, other known and newly detected signatures, highlighting the wealth of termination-associated sequence elements. Intriguingly, orthologous genes with corresponding 3' termini show different termination mechanisms in different bacteria, often matching the dominant mechanism of the respective bacterial species. Analysis of condition-dependent 3' termini revealed some conservation across species, supporting the conjecture that alternative 3' termini can play a role in gene expression regulation. Our resource, available through a user-friendly web server (https://bacterminome.huji.ac.il), provides a platform for studying transcription termination at an unprecedented scope.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118076"},"PeriodicalIF":7.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149214957","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

Divergent interplay between STIM1 and STIM2 sets the efficacy of central synapses. STIM1和STIM2之间的不同相互作用决定了中枢突触的功效。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-16 DOI: 10.1016/j.celrep.2026.118153

Jiangnan Xiao, Jahleel D Torres-Pérez, Eve Gautreaux, A Alejandro Vilcaes, Natali L Chanaday

{"title":"Divergent interplay between STIM1 and STIM2 sets the efficacy of central synapses.","authors":"Jiangnan Xiao, Jahleel D Torres-Pérez, Eve Gautreaux, A Alejandro Vilcaes, Natali L Chanaday","doi":"10.1016/j.celrep.2026.118153","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118153","url":null,"abstract":"Stromal interaction molecules (STIMs) are endoplasmic reticulum resident calcium (Ca2+ sensors that modulate Ca2+ homeostasis. Mammals express two isoforms, STIM1 and STIM2, but whether they serve redundant or distinct roles in neurotransmission remains poorly defined. Using Ca2+ imaging and electrophysiology in hippocampal neurons lacking STIM1, STIM2, or both, we examined presynaptic and postsynaptic functions of STIMs at excitatory and inhibitory synapses. Both isoforms redundantly activated store-operated Ca2+ entry and amplified presynaptic Ca2+ influx, sustaining neurotransmitter release by expanding the readily releasable pool of synaptic vesicles and accelerating vesicle replenishment. These presynaptic roles were synapse specific: STIM1 predominantly supported excitatory synapses, whereas STIM2 was critical for the inhibitory counterparts. Postsynaptically, STIM1 and STIM2 exerted opposing effects on glutamate and GABA receptor levels, such that simultaneous loss of both isoforms rescued postsynaptic function. Together, the findings show that STIM1 and STIM2 differentially tune synaptic efficacy according to synapse type and subcellular compartment.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118153"},"PeriodicalIF":7.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206549","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

Early-life high-fat diet accelerates the development of vagal satiation signaling and predisposes females to overconsumption. 生命早期的高脂肪饮食加速了迷走神经饱腹信号的发展，使女性容易过度进食。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-16 DOI: 10.1016/j.celrep.2026.118113

Meaghan McCoy, Ciorana Roman-Ortiz, Jason Perez, Lindsey A Schier, Anna K Kamitakahara

{"title":"Early-life high-fat diet accelerates the development of vagal satiation signaling and predisposes females to overconsumption.","authors":"Meaghan McCoy, Ciorana Roman-Ortiz, Jason Perez, Lindsey A Schier, Anna K Kamitakahara","doi":"10.1016/j.celrep.2026.118113","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118113","url":null,"abstract":"Overconsumption of foods rich in fats, sugars, and calories is a major contributing factor to increased risk for cardiometabolic disease. Ingestive experience with these foods can begin early in children, yet there is limited understanding of the impact of early life nutrition on the development of vagal afferent neurons necessary for coordinating appetitive and satiating behaviors. To address this gap, mice reared on a chow diet (control) were compared to those reared on a high-fat diet (HFDEARLY). We demonstrate that the vagally mediated satiation response to cholecystokinin (CCK) does not mature until adolescence in chow-reared mice. However, HFDEARLY exposure triggers a precocious maturation of this response, accompanied by transcriptomic changes in the nodose ganglion. Durable changes in orosensory processing and appetitive behaviors are also evident in adult female HFDEARLY mice, which consume more lipid and calorie-dense liquid diet than controls, suggesting a lasting, sex-specific vulnerability to overconsumption of palatable, energy-dense foods.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":" ","pages":"118113"},"PeriodicalIF":7.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206615","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 lysis mechanism of the haloarchaeal virus HFTV1. 盐古细菌病毒HFTV1的裂解机制。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-16 DOI: 10.1016/j.celrep.2026.118117

Bastiaan P Kuiper, Marco P A van Tilburg, Leonard E Bäcker, Sourav Maity, Yogy S Ariyanto, Joshua G Petters, Zaloa Aguirre-Sourrouille, Jeroen G Nijland, Harma Karsens, Greetje A Berrelkamp-Lahpor, Colin Tittes, Johanna Wiechert, Julia Frunzke, Bertram Daum, Wouter H Roos, Siewert-J Marrink, Tessa E F Quax

{"title":"The lysis mechanism of the haloarchaeal virus HFTV1.","authors":"Bastiaan P Kuiper, Marco P A van Tilburg, Leonard E Bäcker, Sourav Maity, Yogy S Ariyanto, Joshua G Petters, Zaloa Aguirre-Sourrouille, Jeroen G Nijland, Harma Karsens, Greetje A Berrelkamp-Lahpor, Colin Tittes, Johanna Wiechert, Julia Frunzke, Bertram Daum, Wouter H Roos, Siewert-J Marrink, Tessa E F Quax","doi":"10.1016/j.celrep.2026.118117","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118117","url":null,"abstract":"Tailed bacteriophages can lyse their host with help of the holin-endolysin system. However, for archaeal tailed viruses (arTVs), whose archaeal hosts have a fundamentally different cell envelope, lysis mechanisms are unknown. In this study, we use the model archaeal virus-host system: Haloferax tailed virus 1 (HFTV1), which infects the methanobacteriote Haloferax gibbonsii LR2-5. We identified and characterized the lysis protein GP33, a small membrane protein that has no sequence homology with bacterial holins. Overexpression resulted in cell lysis, and the protein forms foci near the cell envelope. Molecular dynamics simulation suggests that it forms pores from which the lipids are repelled, which might result in cell lysis. Indeed, atomic force microscopy (AFM) showed that GP33 forms pores in membranes, which lead to complete membrane disruption at higher concentrations. With this work, we gain insight into a lysis mechanism from a tailed archaeal virus at the molecular level.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118117"},"PeriodicalIF":7.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206572","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

NAD⁺ precursor treatment prevents cardiomyopathy but disrupts erythroid maturation in mitochondrial progeria. NAD+前体治疗可预防心肌病，但会破坏线粒体早衰症的红细胞成熟。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-16 DOI: 10.1016/j.celrep.2026.118179

Nahid A Khan, Kati Ahlqvist, Swagat Pradhan, Juan Landoni, Christopher Jackson, Aleksandra Zhaivoron, Riikka Kivelä, Liliya Euro, Anu Suomalainen

引用次数: 0