Science Advances最新文献

{"title":"Retroviral insertions contributed to the divergence of human and chimpanzee brains","authors":"Patricia Gerdes,&nbsp;Ofelia Karlsson,&nbsp;Raquel Garza,&nbsp;Diahann A. M. Atacho,&nbsp;PingHsun Hsieh,&nbsp;Bharat Prajapati,&nbsp;DongAhn Yoo,&nbsp;Chandramouli Muralidharan,&nbsp;Anita Adami,&nbsp;Carrie Davis-Hansson,&nbsp;Emily M. Johansson,&nbsp;Yogita Sharma,&nbsp;Laura Castilla-Vallmanya,&nbsp;Wiktor West,&nbsp;Meghna Vinod,&nbsp;Lucian Domitrovic,&nbsp;Pia A. Johansson,&nbsp;Jenny Johansson,&nbsp;Christopher H. Douse,&nbsp;Chandrasekhar Kanduri,&nbsp;Patric Jern,&nbsp;Evan E. Eichler,&nbsp;Johan Jakobsson","doi":"10.1126/sciadv.aeg5791","DOIUrl":"10.1126/sciadv.aeg5791","url":null,"abstract":"<div >Over the past 5 to 7 million years, humans and chimpanzees have diverged in brain size, structure, and cognition despite high conservation of protein-coding genes. However, retroviral infections within host genomes have introduced numerous species-specific regulatory elements. Chimpanzees harbor lineage-specific PTERV1 endogenous retroviruses that are absent in humans, but their role in brain evolution has remained unclear. We performed an epigenomic analysis of PTERV1 insertions in chimpanzee neural organoids and found they are heavily DNA methylated, forming over 150 species-specific heterochromatin domains with the potential to influence gene regulation. We identified a chimpanzee-specific insertion on chromosome 19 that silences the long noncoding RNA <i>LINC00662</i> through DNA methylation spreading. CRISPR-mediated deletion of this PTERV1 restored <i>LINC00662</i> expression in chimpanzee induced pluripotent stem cells. We show that <i>LINC00662</i>, a human-specific transcript expressed during brain development, plays a role in neuronal maturation, axon outgrowth, and neural organoid development. These findings reveal a mechanism by which endogenous retroviral insertions contributed to human-chimpanzee brain divergence.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 43","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.aeg5791","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149232709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hemolymph pressure-mediated friction in the tarsus of the desert locust (Schistocerca gregaria)","authors":"Jiahui Zhao,&nbsp;Zhendong Dai,&nbsp;Stanislav N. Gorb,&nbsp;Chuchu Li","doi":"10.1126/sciadv.aeg9427","DOIUrl":"10.1126/sciadv.aeg9427","url":null,"abstract":"<div >The desert locust (<i>Schistocerca gregaria</i>) performs high-acceleration jumps within milliseconds, relying not only on powerful muscles and spring-loaded hindlegs, but also on precise tarsi-substrate interactions. Although the mechanics of jumping have been extensively studied, the mechanisms enabling rapid attachment and detachment remain poorly understood. Here, we characterize the frictional properties of hindleg tarsi under controlled low-speed contact conditions targeting selected loading features associated with jumping. We hypothesize that locusts coordinate tarsal cuticular structures with internal hemolymph pressure to modulate contact mechanics. Using high-speed videography, a suite of advanced microscopic techniques, biomechanical experiments, and biomimetic prototypes, we provide evidence that hemolymph pressure modulates tarsal stiffness and acts together with structural asymmetry to produce direction-dependent frictional responses. This interplay may contribute to adaptive friction tuning associated with jumping. Our findings advance the understanding of locust locomotor biomechanics and suggest design principles for robotic systems requiring rapid and controllable surface engagement.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 43","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.aeg9427","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149233113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using initial states to identify successful El Niño–Southern Oscillation forecasts 1 year in advance","authors":"Nandini Ramesh,&nbsp;Mandy B. Freund,&nbsp;Damien B. Irving,&nbsp;Dougal T. Squire,&nbsp;Carly R. Tozer,&nbsp;Didier P. Monselesan,&nbsp;Tess Parker,&nbsp;Annette Stellema,&nbsp;James S. Risbey","doi":"10.1126/sciadv.aeg8654","DOIUrl":"10.1126/sciadv.aeg8654","url":null,"abstract":"<div >El Niño–Southern Oscillation (ENSO) is the primary source of climate predictability on seasonal and longer timescales over much of the globe, but predicting its phase beyond 9 months has remained challenging. Here, we leverage an underappreciated factor in ENSO forecasting: the substantial variation in forecast skill based on the ENSO phase at the time a forecast is issued. Our analysis of transitions between ENSO phases in a dynamical hindcast dataset demonstrates that this variation markedly exceeds intermodel differences in predictive capability. Forecasts initialized during La Niña conditions perform best, with three models correctly predicting transitions to El Niño 1 year in advance over 70% of the time. We present our findings in a simple framework that allows decision-makers to assess the likelihood of a forecast being correct on the basis of the current ENSO state. Applied effectively, these findings could improve long-lead ENSO forecasting strategies, enhancing global risk management.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 43","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.aeg8654","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149232706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TET2-driven activation of AGO2 links epigenetic remodeling to myeloid commitment and leukemia","authors":"Aleksey Lazarenkov,&nbsp;Gemma Valcárcel,&nbsp;Alba Martinez,&nbsp;Clara Berenguer,&nbsp;Anna V. López-Rubio,&nbsp;Mireia Obiols,&nbsp;Claudia Fontanet,&nbsp;Ana Barba,&nbsp;Juan José Rodríguez-Sevilla,&nbsp;Gregoire Stik,&nbsp;Irmela Jeremias,&nbsp;Pablo Menendez,&nbsp;José Luis Sardina","doi":"10.1126/sciadv.aee5701","DOIUrl":"10.1126/sciadv.aee5701","url":null,"abstract":"<div >DNA methylation dynamics shape hematopoietic differentiation and leukemogenesis, yet how the dioxygenase TET2—frequently mutated in myeloid malignancies—directs lineage-specific regulatory programs remains unclear. Here, we integrated DNA methylation, chromatin accessibility, three-dimensional (3D) genome architecture, transcriptional profiling, and TET2 chromatin occupancy to define TET2-dependent control of human myeloid commitment. We found that TET2-bound regulatory regions gain short- and long-range chromatin interactions and that a distinct subset of distal, enhancer-enriched sites undergoes TET2-driven demethylation and activation. Among these, we identified and functionally validated an <i>AGO2</i> myeloid-specific intragenic enhancer that is frequently hypermethylated in patients with <i>TET2</i>-mutant acute myeloid leukemia. <i>AGO2</i> expression stratifies patient survival, and AGO2 depletion abrogates leukemic engraftment in vivo. These findings uncover a TET2-AGO2 regulatory axis that integrates epigenetic remodeling, 3D genome reorganization, and leukemic fitness, and they highlight AGO2 as a potential biomarker and therapeutic target in myeloid leukemia.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 43","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.aee5701","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149232712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lineage-specific and gestational age–dependent DNA methylation programming orchestrates human placental development","authors":"Shanru Yi,&nbsp;Jing Xiao,&nbsp;Ruixue Wang,&nbsp;Mengting Wang,&nbsp;Chunyan Le,&nbsp;Guang Yang,&nbsp;Shanshan Yi,&nbsp;Wenju Liu,&nbsp;Hong Wang,&nbsp;Xiaocui Li,&nbsp;Xiaoyu Liu,&nbsp;Kai Wang,&nbsp;Cizhong Jiang,&nbsp;Shaorong Gao,&nbsp;Jiayu Chen","doi":"10.1126/sciadv.aee0560","DOIUrl":"10.1126/sciadv.aee0560","url":null,"abstract":"<div >The human placenta is essential for pregnancy, yet the dynamic regulation of its DNA methylome during development remains poorly understood. To address this, we generated a single base–resolution DNA methylation atlas of human placental trophoblasts across gestation. We identified a lineage-specific methylation program established immediately after implantation, followed by gestational age–dependent methylation accumulation. This program acted as a developmental barrier that coordinated placental maturation and immune homeostasis. By integrating histone modifications and functional perturbations, we revealed a temporal dynamic between H3K27me3 and DNA methylation that silenced proinflammatory loci and a switch from H3K9me3 to DNA methylation at repeat elements to maintain genome stability. Aberrant methylation in preterm placentas underscored the physiological importance of methylation regulation. Using human trophoblast stem cells, we demonstrated that <i>DNMT1</i> was critically required for maintaining trophoblast methylome integrity and self-renewal, while the DNMT3 family were equally essential for trophoblast survival. Overall, we established a placenta-specific epigenetic framework for human trophoblast development.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 43","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.aee0560","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149232716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morphological intelligence for dynamic aerial interactions","authors":"Yongkang Jiang,&nbsp;Junjin Li,&nbsp;Shuyu Meng,&nbsp;Yanmin Zhou,&nbsp;Bin He,&nbsp;Jamie Paik","doi":"10.1126/sciadv.aeg4557","DOIUrl":"10.1126/sciadv.aeg4557","url":null,"abstract":"<div >Biological flyers achieve ecological dominance not through flight alone, but by seamlessly integrating aerial locomotion with forceful physical interactions, including snatching prey, perching on irregular surfaces, and operating across diverse media. Translating this agility into aerial robotics demands reconciling a fundamental conflict: impulsive, high-force actions destabilize the flight platform. Here, we present a bio-inspired unmanned aerial vehicle (UAV) equipped with a mechanically intelligent impulsive limb that resolves this tradeoff through physical decoupling. An asymmetric bistable impulse module delivers a 2.3-fold extension within 70 ms, while a soft-linkage architecture reduces the transmission of impulsive interaction forces to the airframe. For the tested seven-segment configuration, intrinsic geometric tolerance corresponds to a passive vertical accommodation range of approximately 70% of the fully deployed arm length, reducing the need for precise altitude regulation within the tested range. We demonstrate the system’s multimodal capacity through dynamic in-flight snatching, energy-efficient perching, high-impact solid fracture, and cross-medium capture in viscous fluids, establishing a new paradigm for UAVs executing physically demanding tasks in complex environments.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 43","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.aeg4557","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149233083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histone methyltransferase NSD2 shapes CD8+ T cell fates through the H3K36me2-Zbtb20 axis","authors":"Shijie Yuan,&nbsp;Yifan Xu,&nbsp;Huicheng Liu,&nbsp;Ying Xue,&nbsp;Mengdi Zhu,&nbsp;Xiaorong Xie,&nbsp;Xuwei Wu,&nbsp;Yuting Xia,&nbsp;Lin Li,&nbsp;Yuan Luo,&nbsp;Zehan Huang,&nbsp;Xiangping Yang,&nbsp;Huiyun Du,&nbsp;Ran He","doi":"10.1126/sciadv.aee9670","DOIUrl":"10.1126/sciadv.aee9670","url":null,"abstract":"<div >CD8⁺ T cells, as the most important cytolytic cells in adaptive immunity, can differentiate into distinct subpopulations with specific functions and fates. During this process, CD8⁺ T cells exhibit substantial plasticity in their differentiation trajectory. Notably, epigenetic regulation has emerged as a pivotal mechanism to govern T cell fate decisions. In this study, we demonstrate that the histone methyltransferase NSD2 critically regulates CD8⁺ T cell differentiation during acute viral infection. While NSD2 deficiency enhances the early expansion of activated CD8⁺ T cells, it severely compromises their survival fitness during the contraction phase, leading to a disproportionate collapse of the antigen-specific pool and limiting the establishment of robust long-lived memory. Mechanistically, this defect is driven by the disruption of the H3K36me2-<i>Zbtb20</i> regulatory axis. Furthermore, we show that in the absence of NSD2, CD8⁺ T cells in tumor exhibit an increased proportion but dysfunctional resident memory T cell phenotype. Collectively, our findings highlight a critical role for NSD2 in providing more mechanistic insights into how epigenetic mechanisms fine-tune T cell differentiation.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 43","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.aee9670","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149233104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PhagoID: Quantitative in situ proximity labeling defines the proteomes of bead- and microbe-containing phagosome lumina across species, maturation, and immune activation","authors":"Benjamin L. Allsup,&nbsp;Supriya Gharpure,&nbsp;Cal Gunnarsson,&nbsp;Mateo L. Stagg,&nbsp;Bryan D. Bryson","doi":"10.1126/sciadv.aee3876","DOIUrl":"10.1126/sciadv.aee3876","url":null,"abstract":"<div >The phagosome is an immune organelle that integrates signals from diverse cargos to drive pathogen killing, tissue homeostasis, and antigen presentation. How this compartment coordinates such diverse functions remains incompletely understood. A comprehensive view of phagosomal composition across cell states and perturbations could accelerate insight into its regulation. Here, we establish PhagoID, a modular proximity labeling approach that enables in situ proteomic profiling of the phagosome lumen in living cells. Applying PhagoID to murine and human macrophages, we define conserved and species-specific phagosomal proteomes that include both canonical lysosomal components and unexpected contributors from nuclear, mitochondrial, and endoplasmic reticulum (ER) compartments. Integrating these proteomes with 25 genome-scale CRISPR screens of phagosomal phenotypes, we identify a network of lumenal proteins that regulate cargo uptake, acidification, antigen presentation, and microbial control highlighting previously unrecognized phagosomal effectors. We next adapt PhagoID to profile the microbe-containing phagosome and compare the sterile bead-containing phagosome to the <i>Escherichia coli</i>–containing phagosome, demonstrating a modest <i>E. coli</i> signature of phagosome remodeling. Comparative analyses further reveal that loss of LAMP1 enhances recruitment of ER-derived proteins to the phagosome, whereas loss of TFEB minimally perturbs the lumenal proteome despite its role in lysosomal biogenesis. Last, cytokine stimulation remodels the phagosome lumen to enrich for proteins involved in antigen presentation and antimicrobial activity in response to type I and II interferons. These data demonstrate that PhagoID delivers a high-confidence, quantitative, and integrative map of the phagosome lumen, revealing previously unidentified axes of organellar communication and regulatory control in innate immunity.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 43","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.aee3876","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149233114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Opposing cell-type preferences for binding and replication shape influenza A virus infection in human airways","authors":"Josephine von Kempis,&nbsp;Marie O. Pohl,&nbsp;Elisabeth Gaggioli,&nbsp;Cyrille Niklaus,&nbsp;Alexandra Trkola,&nbsp;Geert-Jan Boons,&nbsp;Robert P. de Vries,&nbsp;Silke Stertz","doi":"10.1126/sciadv.aei5782","DOIUrl":"10.1126/sciadv.aei5782","url":null,"abstract":"<div >Influenza A viruses (IAVs) pose a threat to human health. Although receptor specificity, polymerase adaptation, and airway tropism have been studied extensively, it remains unresolved how they combine to shape tropism in airway epithelia. Here, we show that avian IAVs infect ciliated and secretory cells but preferentially bind to ciliated cells because of higher apical α2,3-linked sialic acid levels. As replication levels are comparable between cell types, this translates into overall preference for ciliated cells. Human IAVs also preferentially bind to ciliated cells despite comparable α2,6-linked sialic acid abundance. Instead, they show higher viral RNA and protein levels in secretory cells, linked to their compatibility with human ANP32 proteins and modestly higher ANP32A/B expression in this cell type, resulting in equal infection levels across cell types. Our findings redefine IAV tropism in the human airway as a stage-resolved process shaped by the interplay between apical glycans, viral binding, polymerase cofactor compatibility, and cell-type–specific replication capacity, moving beyond receptor-centric models.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 43","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.aei5782","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149232696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Nematostella synaptonemal complex mediates divergent and sex-specific meiotic programs","authors":"Stefanie Williams,&nbsp;Jennifer Gardner,&nbsp;Stephanie H. Nowotarski,&nbsp;Matthew C. Gibson","doi":"10.1126/sciadv.aei0758","DOIUrl":"10.1126/sciadv.aei0758","url":null,"abstract":"<div >Throughout eukaryotes, the synaptonemal complex (SC) is a supramolecular structure essential for meiotic chromosome dynamics and sexual reproduction. While metazoan SC proteins display substantial sequence divergence, the lack of functional analyses beyond bilaterian models has obscured a mechanistic understanding of SC evolution. Here, we report that the sea anemone <i>Nematostella vectensis</i> exhibits synapsis of homologous chromosomes in a classic zipper-like manner and expresses at least eight orthologs of 10 known vertebrate SC proteins. Unexpectedly, mutagenesis of the core SC components <i>sycp1</i>, <i>syce2</i>, and <i>sycp3</i> resulted in divergent and sexually dimorphic phenotypes, indicating the functional diversification of these conserved factors. Combined, these findings challenge the assumption that the conservation of protein sequence or ultrastructure implies mechanistic homology.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"12 43","pages":""},"PeriodicalIF":13.9,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.aei0758","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149232698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}