CellPub Date : 2025-06-17DOI: 10.1016/j.cell.2025.05.033
Rebecka J. Sepela, Hao Jiang, Yern-Hyerk Shin, Tessa L. Hautala, Jon Clardy, Ryan E. Hibbs, Nicholas W. Bellono
{"title":"Environmental microbiomes drive chemotactile sensation in octopus","authors":"Rebecka J. Sepela, Hao Jiang, Yern-Hyerk Shin, Tessa L. Hautala, Jon Clardy, Ryan E. Hibbs, Nicholas W. Bellono","doi":"10.1016/j.cell.2025.05.033","DOIUrl":"https://doi.org/10.1016/j.cell.2025.05.033","url":null,"abstract":"Microbial communities coat nearly every surface in the environment and have co-existed with animals throughout evolution. Whether animals exploit omnipresent microbial cues to navigate their surroundings is not well understood. Octopuses use “taste-by-touch” chemotactile receptors (CRs) to explore the seafloor, but how they distinguish meaningful surfaces from the rocks and crevices they encounter is unknown. Here, we report that secreted signals from microbiomes of ecologically relevant surfaces activate CRs to guide octopus behavior. Distinct molecules isolated from individual bacterial strains located on prey or eggs bind single CRs in subtly different structural conformations to elicit specific mechanisms of receptor activation, ion permeation and signal transduction, and maternal care and predation behavior. Thus, microbiomes on ecological surfaces act at the level of primary sensory receptors to inform behavior. Our study demonstrates that uncovering interkingdom interactions is essential to understanding how animal sensory systems evolved in a microbe-rich world.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"14 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144305491","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}
CellPub Date : 2025-06-17DOI: 10.1016/j.cell.2025.05.011
Masaki Yagi, Gracia Bonilla, Michael S. Hoetker, Nikolaos Tsopoulidis, Joy E. Horng, Chuck Haggerty, Alexander Meissner, Ruslan I. Sadreyev, Hanno Hock, Konrad Hochedlinger
{"title":"Bivalent chromatin instructs lineage specification during hematopoiesis","authors":"Masaki Yagi, Gracia Bonilla, Michael S. Hoetker, Nikolaos Tsopoulidis, Joy E. Horng, Chuck Haggerty, Alexander Meissner, Ruslan I. Sadreyev, Hanno Hock, Konrad Hochedlinger","doi":"10.1016/j.cell.2025.05.011","DOIUrl":"https://doi.org/10.1016/j.cell.2025.05.011","url":null,"abstract":"Developmental gene expression is regulated by the dynamic interplay of histone H3 lysine 4 (H3K4) and histone H3 lysine 27 (H3K27) methylation, yet the physiological roles of these epigenetic modifications remain incompletely understood. Here, we show that mice depleted for all forms of H3K4 methylation, using a dominant histone H3-lysine-4-to-methionine (H3K4M) mutation, succumb to a severe loss of all major blood cell types. H3K4M-expressing hematopoietic stem cells (HSCs) and committed progenitors are present at normal numbers, indicating that H3K4 methylation is dispensable for HSC maintenance and commitment but essential for progenitor cell maturation. Mechanistically, we reveal that H3K4 methylation opposes the deposition of repressive H3K27 methylation at differentiation-associated genes enriched for a bivalent (i.e., H3K4/H3K27-methylated) chromatin state in HSCs and progenitors. Indeed, by concomitantly suppressing H3K27 methylation in H3K4-methylation-depleted mice, we rescue the acute lethality, hematopoietic failure, and gene dysregulation. Our results provide functional evidence for the interaction between two crucial chromatin marks in mammalian tissue homeostasis.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"11 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144305487","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}
CellPub Date : 2025-06-17DOI: 10.1016/j.cell.2025.05.027
Emanuele Pitino, Anna Pascual-Reguant, Felipe Segato-Dezem, Kellie Wise, Irepan Salvador-Martinez, Helena Lucia Crowell, Maycon Marção, Max Ruiz, Elise Courtois, William F. Flynn, Santhosh Sivajothi, Emily Soja, Ginevra Caratù, German Atzin Mora-Roldan, B. Kate Dredge, Yutian Liu, Hannah Chasteen, Monika Mohenska, Juan C. Nieto, Raymond K.H. Yip, Luciano G. Martelotto
{"title":"STAMP: Single-cell transcriptomics analysis and multimodal profiling through imaging","authors":"Emanuele Pitino, Anna Pascual-Reguant, Felipe Segato-Dezem, Kellie Wise, Irepan Salvador-Martinez, Helena Lucia Crowell, Maycon Marção, Max Ruiz, Elise Courtois, William F. Flynn, Santhosh Sivajothi, Emily Soja, Ginevra Caratù, German Atzin Mora-Roldan, B. Kate Dredge, Yutian Liu, Hannah Chasteen, Monika Mohenska, Juan C. Nieto, Raymond K.H. Yip, Luciano G. Martelotto","doi":"10.1016/j.cell.2025.05.027","DOIUrl":"https://doi.org/10.1016/j.cell.2025.05.027","url":null,"abstract":"Single-cell RNA sequencing has revolutionized our understanding of cellular diversity but remains constrained by scalability, high costs, and the destruction of cells during analysis. To overcome these challenges, we developed STAMP (single-cell transcriptomics analysis and multimodal profiling), a highly scalable approach for the profiling of single cells. By leveraging transcriptomics and proteomics imaging platforms, STAMP eliminates sequencing costs, enabling cost-efficient single-cell genomics of millions of cells. Immobilizing (stamping) cells in suspension onto imaging slides, STAMP supports multimodal (RNA, protein, and H&E) profiling, while retaining cellular structure and morphology. We demonstrate STAMP’s versatility by profiling peripheral blood mononuclear cells, cell lines, and stem cells. We highlight the capability of STAMP to identify ultra-rare cell populations, simulate clinical applications, and show its utility for large-scale perturbation studies. In total, we present data for 10,962,092 high-quality cells/nuclei and 6,030,429,954 transcripts. STAMP makes high-resolution cellular profiling more accessible, scalable, and affordable.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"153 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144305488","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}
CellPub Date : 2025-06-17DOI: 10.1016/j.cell.2025.05.034
Yi Xian Er, Soo Ching Lee, Chioma Aneke, Sean Conlan, Azdayanti Muslim, Clay Deming, You Che, Nan Jiun Yap, Mian Zi Tee, Nurmanisha Abdull-Majid, Shezryna Shahrizal, Kin Fon Leong, Jungmin Han, Zeyang Shen, Leslie Thian Lung Than, Morgan Park, Izandis Mohd Sayed, Amir Seyedmousavi, Heidi H. Kong, Yvonne Ai Lian Lim
{"title":"Trichophyton concentricum fungal infections and skin microbiomes of Indigenous Peninsular Malaysians","authors":"Yi Xian Er, Soo Ching Lee, Chioma Aneke, Sean Conlan, Azdayanti Muslim, Clay Deming, You Che, Nan Jiun Yap, Mian Zi Tee, Nurmanisha Abdull-Majid, Shezryna Shahrizal, Kin Fon Leong, Jungmin Han, Zeyang Shen, Leslie Thian Lung Than, Morgan Park, Izandis Mohd Sayed, Amir Seyedmousavi, Heidi H. Kong, Yvonne Ai Lian Lim","doi":"10.1016/j.cell.2025.05.034","DOIUrl":"https://doi.org/10.1016/j.cell.2025.05.034","url":null,"abstract":"Recent outbreaks of multidrug-resistant fungi infecting human skin emphasize the importance of understanding fungal pathophysiology and spread. In efforts to address health concerns with various Indigenous Peninsular Malaysians (Orang Asli [OA]), tinea imbricata—a <em>Trichophyton concentricum</em> fungal skin infection—emerged as a particular concern. We investigated the etiology and transmission of tinea imbricata by culturing, testing antifungal sensitivities, and sequencing <em>T. concentricum</em> isolates in remote OA villages. Among regionally conserved isolates, we identified the emergence of terbinafine-resistant <em>T. concentricum</em> microbiologically and genomically. Investigating the skin microbiomes of 82 Indigenous OA, we found unique microbiota and lower relative abundances of bacterial commensals (<em>Cutibacterium acnes</em>, <em>Staphylococcus epidermidis</em>) among OA versus Malaysian and US urban populations, emphasizing how understudied populations provide unprecedented knowledge on host-microbiome co-evolution. These findings provide valuable insights into clinical, microbiological, and genomic features of chronic fungal skin infections, offering the potential to inform strategies to address drug resistance and effective therapy.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"6 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144305489","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}
CellPub Date : 2025-06-17DOI: 10.1016/j.cell.2025.05.029
Marcel S. Woo, Johannes Brand, Lukas C. Bal, Manuela Moritz, Mark Walkenhorst, Vanessa Vieira, Inbal Ipenberg, Nicola Rothammer, Man Wang, Batuhan Dogan, Desirée Loreth, Christina Mayer, Darwin Nagel, Ingrid Wagner, Lena Kristina Pfeffer, Peter Landgraf, Marco van Ham, Kuno M.-J. Mattern, Ingo Winschel, Noah Frantz, Manuel A. Friese
{"title":"The immunoproteasome disturbs neuronal metabolism and drives neurodegeneration in multiple sclerosis","authors":"Marcel S. Woo, Johannes Brand, Lukas C. Bal, Manuela Moritz, Mark Walkenhorst, Vanessa Vieira, Inbal Ipenberg, Nicola Rothammer, Man Wang, Batuhan Dogan, Desirée Loreth, Christina Mayer, Darwin Nagel, Ingrid Wagner, Lena Kristina Pfeffer, Peter Landgraf, Marco van Ham, Kuno M.-J. Mattern, Ingo Winschel, Noah Frantz, Manuel A. Friese","doi":"10.1016/j.cell.2025.05.029","DOIUrl":"https://doi.org/10.1016/j.cell.2025.05.029","url":null,"abstract":"Inflammation, aberrant proteostasis, and energy depletion are hallmarks of neurodegenerative diseases such as multiple sclerosis (MS). However, the interplay between inflammation, proteasomal dysfunction in neurons, and its consequences for neuronal integrity remains unclear. Using transcriptional, proteomic, and functional analyses of proteasomal subunits in inflamed neurons, we found that interferon-γ-mediated induction of the immunoproteasome subunit, proteasome 20S beta 8 (PSMB8) impairs the proteasomal balance, resulting in reduced proteasome activity. This reduction causes the accumulation of phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a key metabolic regulator, leading to enhanced neuronal glycolysis, reduced pentose phosphate pathway activity, oxidative injury, and ferroptosis. Neuron-specific genetic and systemic pharmacological targeting of PSMB8 or PFKFB3 protected neurons <em>in vitro</em> and in a mouse model of MS. Our findings provide a unifying explanation for proteasomal dysfunction in MS and possibly other neurodegenerative diseases, linking inflammation to metabolic disruption, and presenting an opportunity for targeted neuroprotective therapies.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"8 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144305490","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}
CellPub Date : 2025-06-17DOI: 10.1016/j.cell.2025.05.028
Xiaofei Du, Maheen Alam, Kamil Witek, Lesley Milnes, James Houghton, Xiao Lin, Hee-Kyung Ahn, Yu Zhang, Fuhao Cui, Wenxian Sun, Jonathan D.G. Jones, Hailong Guo
{"title":"Interfamily co-transfer of sensor and helper NLRs extends immune receptor functionality between angiosperms","authors":"Xiaofei Du, Maheen Alam, Kamil Witek, Lesley Milnes, James Houghton, Xiao Lin, Hee-Kyung Ahn, Yu Zhang, Fuhao Cui, Wenxian Sun, Jonathan D.G. Jones, Hailong Guo","doi":"10.1016/j.cell.2025.05.028","DOIUrl":"https://doi.org/10.1016/j.cell.2025.05.028","url":null,"abstract":"Plant nucleotide-binding, leucine-rich repeat (NLR) immune receptors recognize pathogen effectors and activate defense. NLR genes can be non-functional in distantly related plants (restricted taxonomic functionality, RTF). Here, we enable Solanaceae NLR gene function in rice, soybean, and <em>Arabidopsis</em> by co-delivering sensor NLR genes with their cognate NLR required for cell death (NRC)-type helper NLRs. In soybean protoplasts and in <em>Arabidopsis</em> plants, <em>Solanum americanum</em> Rpi-amr1, Rpi-amr3, and pepper Bs2 sensor NLRs confer cognate effector responsiveness if co-expressed with NRC helper NLRs. Rice carrying pepper Bs2 and NRCs recognizes the conserved effector, AvrBs2, and resists an important pathogen, <em>Xanthomonas oryzae</em> pv. <em>oryzicola</em>, for which no resistance gene is available in rice. Rice lines carrying sensor and helper NLR genes otherwise resemble wild type, with unaltered basal resistance or field fitness. Thus, interfamily co-transfer of sensor and helper NLRs can broaden the utility of sensor NLRs, extending the tools available to control diseases of rice, soybean, <em>Brassica</em>, and other crops.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"6 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144305485","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}
{"title":"Adaptive radiation and social evolution of the ants","authors":"Joel Vizueta, Zijun Xiong, Guo Ding, Rasmus S. Larsen, Hao Ran, Qionghua Gao, Josefin Stiller, Wei Dai, Wei Jiang, Jie Zhao, Chunxue Guo, Xiafang Zhang, Dashuang Zuo, Wenjiang Zhong, Morten Schiøtt, Chengyuan Liu, Hailin Zhang, Xueqin Dai, Ignasi Andreu, Yue Shi, Guojie Zhang","doi":"10.1016/j.cell.2025.05.030","DOIUrl":"https://doi.org/10.1016/j.cell.2025.05.030","url":null,"abstract":"Ants originated over 150 million years ago through an irreversible transition to superorganismal colony life. Comparative analyses of 163 ant genomes, including newly generated whole-genome sequences of 145 ant species, reveal extensive genome rearrangements correlated with speciation rates. Meanwhile, conserved syntenic blocks are enriched with co-expressed genes involved in basal metabolism and caste differentiation. Gene families related to digestion, endocrine signaling, cuticular hydrocarbon synthesis, and chemoreception expanded in the ant ancestor, while many caste-associated genes underwent positive selection in the formicoid ancestor. Elaborations and reductions of queen-worker dimorphism and other social traits left convergent signatures of intensified or relaxed selection in conserved signaling and metabolic pathways, suggesting that a core gene set was used to diversify organizational complexity. Previously uncharacterized genetic regulators of caste development were confirmed by functional experiments. This study reconstructs the genetic underpinning of social traits and their integration within gene-regulatory networks shaping caste phenotypes.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"22 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144296301","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}
CellPub Date : 2025-06-13DOI: 10.1016/j.cell.2025.05.026
Zhicheng Wang, Sahil Kulkarni, Jia Nong, Marco Zamora, Alireza Ebrahimimojarad, Elizabeth Hood, Tea Shuvaeva, Michael Zaleski, Damodar Gullipalli, Emily Wolfe, Carolann Espy, Evguenia Arguiri, Jichuan Wu, Yufei Wang, Oscar A. Marcos-Contreras, Wenchao Song, Vladimir R. Muzykantov, Jinglin Fu, Ravi Radhakrishnan, Jacob W. Myerson, Jacob S. Brenner
{"title":"A percolation phase transition controls complement protein coating of surfaces","authors":"Zhicheng Wang, Sahil Kulkarni, Jia Nong, Marco Zamora, Alireza Ebrahimimojarad, Elizabeth Hood, Tea Shuvaeva, Michael Zaleski, Damodar Gullipalli, Emily Wolfe, Carolann Espy, Evguenia Arguiri, Jichuan Wu, Yufei Wang, Oscar A. Marcos-Contreras, Wenchao Song, Vladimir R. Muzykantov, Jinglin Fu, Ravi Radhakrishnan, Jacob W. Myerson, Jacob S. Brenner","doi":"10.1016/j.cell.2025.05.026","DOIUrl":"https://doi.org/10.1016/j.cell.2025.05.026","url":null,"abstract":"When a material enters the body, it is immediately attacked by hundreds of proteins, organized into complex networks of binding interactions and reactions. How do such complex systems interact with a material, “deciding” whether to attack? We focus on the complement system of ∼40 blood proteins that bind microbes, nanoparticles, and medical devices, initiating inflammation. We show a sharp threshold for complement activation upon varying a fundamental material parameter, the surface density of potential complement attachment points. This sharp threshold manifests at scales spanning single nanoparticles to macroscale pathologies, shown here for diverse engineered and living materials. Computational models show these behaviors arise from a minimal subnetwork of complement, manifesting percolation-type critical transitions in the complement response. This criticality switch explains the “decision” of a complex signaling network to interact with a material.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"26 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278516","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}
{"title":"Senescence-resistant human mesenchymal progenitor cells counter aging in primates","authors":"Jinghui Lei, Zijuan Xin, Ning Liu, Taixin Ning, Ying Jing, Yicheng Qiao, Zan He, Mengmeng Jiang, Yuanhan Yang, Zhiyi Zhang, Liyun Zhao, Jingyi Li, Dongliang Lv, Yupeng Yan, Hui Zhang, Lingling Xiao, Baohu Zhang, Haoyan Huang, Shuhui Sun, Fangshuo Zheng, Guang-Hui Liu","doi":"10.1016/j.cell.2025.05.021","DOIUrl":"https://doi.org/10.1016/j.cell.2025.05.021","url":null,"abstract":"Aging is characterized by a deterioration of stem cell function, but the feasibility of replenishing these cells to counteract aging remains poorly defined. Our study addresses this gap by developing senescence (seno)-resistant human mesenchymal progenitor cells (SRCs), genetically fortified to enhance cellular resilience. In a 44-week trial, we intravenously delivered SRCs to aged macaques, noting a systemic reduction in aging indicators, such as cellular senescence, chronic inflammation, and tissue degeneration, without any detected adverse effects. Notably, SRC treatment enhanced brain architecture and cognitive function and alleviated the reproductive system decline. The restorative effects of SRCs are partly attributed to their exosomes, which combat cellular senescence. This study provides initial evidence that genetically modified human mesenchymal progenitors can slow primate aging, highlighting the therapeutic potential of regenerative approaches in combating age-related health decline.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"609 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278518","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}
{"title":"Fragmented replay of very large environments in the hippocampus of bats","authors":"Tamir Eliav, Shir R. Maimon, Ayelet Sarel, Shaked Palgi, Liora Las, Nachum Ulanovsky","doi":"10.1016/j.cell.2025.05.024","DOIUrl":"https://doi.org/10.1016/j.cell.2025.05.024","url":null,"abstract":"The hippocampus is crucial for memory. Memory consolidation is thought to be subserved by hippocampal “replays” of previously experienced trajectories. However, it is unknown how the brain replays long spatial trajectories in very large, naturalistic environments. Here, we investigated this in the hippocampus of bats that were flying prolonged flights in a 200-m-long tunnel. We found many time-compressed replay sequences during sleep and during awake pauses between flights, similar to rodents exploring small environments. Individual neurons fired multiple times per replay, according to their multiple place fields. Surprisingly, replays were highly fragmented, depicting short trajectory pieces covering only ∼6% of the environment size—unlike replays in small setups, which cover most of the environment. This fragmented replay may reflect biophysical or network constraints on replay distance and may facilitate memory chunking for hippocampal-neocortical communication. Overall, hippocampal replay in very large environments is radically different from classical notions of memory reactivation—carrying important implications for hippocampal network mechanisms in naturalistic, real-world environments.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"42 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278517","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}
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