CellPub Date : 2025-10-15DOI: 10.1016/j.cell.2025.09.020
Chuan Qin, Ming-Hao Dong, Luo-Qi Zhou, Yun-Hui Chu, Xiao-Wei Pang, Jia-Yi He, Ke Shang, Jun Xiao, Li Zhu, Huan Ye, Song-Bai Cai, Di Wang, Bi-Tao Bu, Gerd Meyer zu Hörste, Chun-Rui Li, Dai-Shi Tian, Wei Wang
{"title":"Anti-BCMA CAR-T therapy in patients with progressive multiple sclerosis","authors":"Chuan Qin, Ming-Hao Dong, Luo-Qi Zhou, Yun-Hui Chu, Xiao-Wei Pang, Jia-Yi He, Ke Shang, Jun Xiao, Li Zhu, Huan Ye, Song-Bai Cai, Di Wang, Bi-Tao Bu, Gerd Meyer zu Hörste, Chun-Rui Li, Dai-Shi Tian, Wei Wang","doi":"10.1016/j.cell.2025.09.020","DOIUrl":"https://doi.org/10.1016/j.cell.2025.09.020","url":null,"abstract":"Progressive multiple sclerosis (PMS), which is characterized by relentless disease progression, lacks effective treatment. While recent studies have highlighted the importance of B cells in driving compartmentalized central nervous system (CNS) inflammation in PMS pathogenesis, current B cell depletion therapies, such as CD20 monoclonal antibodies, face challenges in targeting plasma cells within the CNS. Here, we treated five patients with PMS (one primary PMS and four secondary PMS) with anti-B cell maturation antigen (BCMA) chimeric antigen receptor T (CAR-T) cell therapy in an ongoing phase 1 clinical trial (<span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>: NCT04561557). Only grade 1 cytokine release syndrome was observed, and all grade ≥3 cytopenias occurred within 40 days post-infusion in all five patients. Meanwhile, we detected plasma cell depletion in CNS compartments, prolonged expansion and relieved exhaustion of CAR-T cells in the cerebrospinal fluid, and attenuation of microglial activation. These findings provided insights into the potential application of anti-BCMA CAR-T therapy for advancing clinical management of PMS.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"53 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145289289","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 : 2025-10-14DOI: 10.1016/j.cell.2025.09.017
Olivier Garsmeur, Simon Rio, Nicolas Pompidor, Anna Lipzen, Catherine Hervouet, Théo Durand, Chris Daum, Yuko Yoshinaga, Mike Butterfield, Alexander Sanchez, George Piperidis, Noa Lincoln, Anna Hale, Jean Yves Hoarau, Yoshifumi Terajima, Prakash Lakshmanan, Erik Sacks, Shailendra Sharma, Marotea Vitrac, Kerrie Barry, Angélique D’Hont
{"title":"The genomic footprints of wild Saccharum species trace domestication, diversification, and modern breeding of sugarcane","authors":"Olivier Garsmeur, Simon Rio, Nicolas Pompidor, Anna Lipzen, Catherine Hervouet, Théo Durand, Chris Daum, Yuko Yoshinaga, Mike Butterfield, Alexander Sanchez, George Piperidis, Noa Lincoln, Anna Hale, Jean Yves Hoarau, Yoshifumi Terajima, Prakash Lakshmanan, Erik Sacks, Shailendra Sharma, Marotea Vitrac, Kerrie Barry, Angélique D’Hont","doi":"10.1016/j.cell.2025.09.017","DOIUrl":"https://doi.org/10.1016/j.cell.2025.09.017","url":null,"abstract":"Sugarcane is a major crop of unclear origins due to its complex polyploid interspecific genome. We analyzed genome ancestries using whole-genome sequence data from 390 representative accessions based on repeated k-mers and chloroplast phylogeny. The results provided evidence that <em>Saccharum officinarum</em> was domesticated in the New Guinea region from the <em>S. robustum</em> wild species and revealed that its genome is a mosaic involving different <em>S. robustum</em> subgroups. We discovered a wild <em>Saccharum</em> contributor to most modern cultivars, likely originating from East Melanesia. We highlighted two early centers of sugarcane diversification associated with human transport, one in continental Asia through hybridization with different <em>S. spontaneum</em> subgroups and one in the Melanesian and Polynesian islands via hybridization with the discovered ancestor and <em>Miscanthus</em>. Finally, we revealed the genome ancestry of modern cultivars, highlighting untapped wild <em>Saccharum</em> diversity as a source of alleles for breeding programs.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"21 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283473","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":"Shaping pit structure in vessel walls sustains xylem hydraulics and grain yield","authors":"Lanjun Zhang, Yihong Gao, Zuopeng Xu, Jingyang Hu, Zhao Wen, Jiaxi Li, Chengxu Gao, Yihua Zhou, Baocai Zhang","doi":"10.1016/j.cell.2025.09.018","DOIUrl":"https://doi.org/10.1016/j.cell.2025.09.018","url":null,"abstract":"Plants have evolved a conduit system with reinforced walls and innovative wall structures that ensure efficient transport of water and nutrients. Vessel pits, fine three-dimensional (3D) cavities in conduit walls, are key determinants of plant hydraulics and growth plasticity. However, their ultrastructure and formation mechanisms are unknown. Here, we reveal the nanoscale 3D structure of pits and the molecular pathway that mediates pit shaping and sustains xylem robustness and grain yield. A quantitative trait locus for pit size (<em>PS1</em>), identified by a genome-wide association study in rice, is a xylan deacetylase that controls pit geometry. An elite PS1 allele modifies xylans to a hypoacetylated state, facilitating their binding to cellulose and maintaining wall coherence around pit boundaries. The elite haplotypes confer rice varieties with enhanced nitrogen transport and grain yield. We thus discover a molecular pathway that boosts xylem hydraulics and crop yield, offering a promising strategy for sustainable agriculture.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"340 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283474","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 : 2025-10-13DOI: 10.1016/j.cell.2025.09.010
Jin Woo Chang, Han Kyu Na, Kyung Won Chang, Chan Wook Park, Do-Hun Kim, Sanghyun Park, Chul-Yong Park, Jang Hyeon Eom, Seung Taek Nam, Ki-Sang Jo, Mi-Young Jo, Sung Kyoung Choi, Hye-Jin Hur, Sarang Kim, Minseok Kim, Dae-Sung Kim, Dong-Youn Hwang, Myoung Soo Kim, Inkyung Jung, Jongwan Kim, Dong-Wook Kim
{"title":"Phase 1/2a clinical trial of hESC-derived dopamine progenitors in Parkinson’s disease","authors":"Jin Woo Chang, Han Kyu Na, Kyung Won Chang, Chan Wook Park, Do-Hun Kim, Sanghyun Park, Chul-Yong Park, Jang Hyeon Eom, Seung Taek Nam, Ki-Sang Jo, Mi-Young Jo, Sung Kyoung Choi, Hye-Jin Hur, Sarang Kim, Minseok Kim, Dae-Sung Kim, Dong-Youn Hwang, Myoung Soo Kim, Inkyung Jung, Jongwan Kim, Dong-Wook Kim","doi":"10.1016/j.cell.2025.09.010","DOIUrl":"https://doi.org/10.1016/j.cell.2025.09.010","url":null,"abstract":"Parkinson’s disease (PD) has long been considered an appropriate candidate for cell replacement therapy. We generated high-purity dopaminergic progenitors (A9-DPCs) from human embryonic stem cells and evaluated their safety and exploratory efficacy in a single-center, open-label, dose-escalation phase 1/2a trial (NCT05887466) for PD patients. Twelve patients with moderate-to-severe PD received bilateral putamen transplantation of low-dose (3.15 million cells; <em>n</em> = 6) or high-dose (6.30 million cells; <em>n</em> = 6) A9-DPC with immunosuppression. No dose-limiting toxicities or graft-related adverse events were observed. At 12 months, off-medication Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III scores and Hoehn and Yahr stage improved, with greater motor improvements in the high-dose group. Dopamine transporter positron emission tomography (PET) imaging showed increased posterior putamen uptake with greater uptake in the high-dose group after transplantation, supporting graft survival. These findings indicate that bilateral transplantation of A9-DPC is safe and may improve parkinsonian motor symptoms in patients with PD.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"28 20 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283475","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 : 2025-10-10DOI: 10.1016/j.cell.2025.09.016
Wout Oosterheert, Micaela Boiero Sanders, Oliver Hofnagel, Peter Bieling, Stefan Raunser
{"title":"Choreography of rapid actin filament disassembly by coronin, cofilin, and AIP1","authors":"Wout Oosterheert, Micaela Boiero Sanders, Oliver Hofnagel, Peter Bieling, Stefan Raunser","doi":"10.1016/j.cell.2025.09.016","DOIUrl":"https://doi.org/10.1016/j.cell.2025.09.016","url":null,"abstract":"Rapid remodeling of actin filament (F-actin) networks is essential for the movement and morphogenesis of eukaryotic cells. The conserved actin-binding proteins coronin, cofilin, and actin-interacting protein 1 (AIP1) act in synergy to promote rapid F-actin network disassembly, but the underlying mechanisms have remained elusive. Here, using cryo-electron microscopy (cryo-EM), we uncover the concerted molecular actions of coronin, cofilin, and AIP1 that lead to actin filament aging and severing. We find that the cooperative binding of coronin allosterically promotes inorganic phosphate release from F-actin and induces filament undertwisting, thereby priming the filament for cofilin binding. Cofilin then displaces coronin from the filament via a strand-restricted cooperative binding mechanism. The resulting cofilactin serves as a high-affinity platform for AIP1, which induces severing by acting as a clamp that disrupts inter-subunit filament contacts. In this “molecular squeezing” mechanism, AIP1 and not cofilin is responsible for filament severing. Our work redefines the role of key disassembly factors in actin dynamics.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"19 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255051","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 : 2025-10-07DOI: 10.1016/j.cell.2025.09.012
Matthew Jensen, Corrine Smolen, Anastasia Tyryshkina, Lucilla Pizzo, Jiawan Sun, Serena Noss, Deepro Banerjee, Matthew Oetjens, Hermela Shimelis, Cora M. Taylor, Vijay Kumar Pounraja, Hyebin Song, Laura Rohan, Emily Huber, Laila El Khattabi, Ingrid van de Laar, Rafik Tadros, Connie R. Bezzina, Marjon van Slegtenhorst, Janneke Kammeraad, Santhosh Girirajan
{"title":"Genetic modifiers and ascertainment drive variable expressivity of complex disorders","authors":"Matthew Jensen, Corrine Smolen, Anastasia Tyryshkina, Lucilla Pizzo, Jiawan Sun, Serena Noss, Deepro Banerjee, Matthew Oetjens, Hermela Shimelis, Cora M. Taylor, Vijay Kumar Pounraja, Hyebin Song, Laura Rohan, Emily Huber, Laila El Khattabi, Ingrid van de Laar, Rafik Tadros, Connie R. Bezzina, Marjon van Slegtenhorst, Janneke Kammeraad, Santhosh Girirajan","doi":"10.1016/j.cell.2025.09.012","DOIUrl":"https://doi.org/10.1016/j.cell.2025.09.012","url":null,"abstract":"Variable expressivity of disease-associated variants implies a role for secondary variants that modify clinical features. We assessed the effects of modifier variants on the clinical outcomes of 2,455 individuals with primary variants. Among 124 families with the 16p12.1 deletion, distinct rare and common variant classes conferred risks for specific developmental features, including short tandem repeats for neurological defects. Network analysis suggested distinct mechanisms involving 16p12.1 genes and secondary variants specific to each proband. Within disease and population cohorts of 976 individuals with the 16p12.1 deletion, we found opposing effects of secondary variants on clinical features across ascertainments. Additional analysis of 1,479 probands with other primary variants, such as the 16p11.2 deletion and <em>CHD8</em> variants, and 1,528 probands without primary variants showed that phenotypic associations differed by primary variant context and were influenced by synergistic interactions between primary and secondary variants. Our study provides a paradigm to dissect the personalized genomic architecture of complex disorders.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"39 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241485","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 : 2025-10-02DOI: 10.1016/j.cell.2025.08.026
Lesia Rodriguez, Lukáš Fiedler, Minxia Zou, Caterina Giannini, Aline Monzer, Dmitrii Vladimirtsev, Marek Randuch, Yongfan Yu, Zuzana Gelová, Inge Verstraeten, Jakub Hajný, Meng Chen, Shutang Tan, Lukas Hoermayer, Lanxin Li, Maria Mar Marques-Bueno, Zainab Quddoos, Gergely Molnár, Ivan Kulich, Yvon Jaillais, Jiří Friml
{"title":"ABP1/ABL3-TMK1 cell-surface auxin signaling targets PIN2-mediated auxin fluxes for root gravitropism","authors":"Lesia Rodriguez, Lukáš Fiedler, Minxia Zou, Caterina Giannini, Aline Monzer, Dmitrii Vladimirtsev, Marek Randuch, Yongfan Yu, Zuzana Gelová, Inge Verstraeten, Jakub Hajný, Meng Chen, Shutang Tan, Lukas Hoermayer, Lanxin Li, Maria Mar Marques-Bueno, Zainab Quddoos, Gergely Molnár, Ivan Kulich, Yvon Jaillais, Jiří Friml","doi":"10.1016/j.cell.2025.08.026","DOIUrl":"https://doi.org/10.1016/j.cell.2025.08.026","url":null,"abstract":"Phytohormone auxin and its directional transport mediate much of the remarkably plastic development of higher plants. Positive feedback between auxin signaling and transport is a prerequisite for (1) self-organizing processes, including vascular tissue formation, and (2) directional growth responses such as gravitropism. Here, we identify a mechanism by which auxin signaling directly targets PIN auxin transporters. Via the cell-surface AUXIN-BINDING PROTEIN1 (ABP1)-TRANSMEMBRANE KINASE 1 (TMK1) receptor module, auxin rapidly induces phosphorylation and thus stabilization of PIN2. Following gravistimulation, initial auxin asymmetry activates autophosphorylation of the TMK1 kinase. This induces TMK1 interaction with and phosphorylation of PIN2, stabilizing PIN2 at the lower root side, thus reinforcing asymmetric auxin flow for root bending. Upstream of TMK1 in this regulation, ABP1 acts redundantly with the root-expressed ABP1-LIKE 3 (ABL3) auxin receptor. Such positive feedback between cell-surface auxin signaling and PIN-mediated polar auxin transport is fundamental for robust root gravitropism and presumably for other self-organizing developmental phenomena.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"114 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204027","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 : 2025-10-02DOI: 10.1016/j.cell.2025.08.037
Kyle Coleman, Nicholas P. Tatonetti
{"title":"Decoding Alzheimer’s disease at the cellular level reveals promising combination therapy","authors":"Kyle Coleman, Nicholas P. Tatonetti","doi":"10.1016/j.cell.2025.08.037","DOIUrl":"https://doi.org/10.1016/j.cell.2025.08.037","url":null,"abstract":"Alzheimer’s disease (AD) has long resisted effective treatments due to its pathological heterogeneity and cell-type-specific regulatory changes. In this issue of <em>Cell</em>, Li et al. leverage single-cell RNA sequencing and drug repurposing to propose a promising combination therapy, validated through real-world evidence and mouse models, that targets multiple AD-relevant cell types.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"60 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204028","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 : 2025-10-02DOI: 10.1016/j.cell.2025.08.033
Cecilia Xi Zhang, Ruby Yun-Ju Huang, Guojun Sheng, Jean Paul Thiery
{"title":"Epithelial-mesenchymal transition","authors":"Cecilia Xi Zhang, Ruby Yun-Ju Huang, Guojun Sheng, Jean Paul Thiery","doi":"10.1016/j.cell.2025.08.033","DOIUrl":"https://doi.org/10.1016/j.cell.2025.08.033","url":null,"abstract":"Epithelial-mesenchymal transition (EMT) is a fundamental mechanism involved in the morphogenesis of metazoans. Through this evolutionarily conserved multi-stage process, cells acquire quasi-epithelial to multiple intermediate morphologies with epithelial and mesenchymal attributes, rarely reaching a complete mesenchymal phenotype. Complex evolutionary-conserved morphogenetic movements in gastrulation are described extensively, as they exemplify the extent of epithelial cell plasticity in the animal kingdom. Nonetheless, a single-gene knockout can modify the mode of gastrulation while achieving the same body plan. Numerous interconnected mechanisms drive different degrees of EMT, including surface receptor signaling, metabolism, and epigenetics. EMT is reactivated in adult tissues during repair and disease, particularly in cancer initiation, progression to metastasis, and refractoriness to treatment. EMT also contributes to dormancy and drug tolerance, leading to minimal residual disease at the origin of recurrences. Multiple EMT states coexist in tumors, creating a dynamic ecosystem for generating an inflammatory microenvironment, stemness, invasion, and metastasis. This review provides an in-depth description of these aspects along with recent controversies and offers new opportunities to further explore the multiple functions of EMT. Examining the potential attributes of EMT in tissue repair, fibrosis, and cancer progression can provide new opportunities for therapeutic intervention.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"23 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204029","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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