Cell reports最新文献_第6页

Host-triggered prophage induction drives Lactiplantibacillus plantarum symbiosis through bacterial lysis. 宿主触发的噬菌体诱导通过细菌裂解驱动植物乳杆菌共生。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-08 DOI: 10.1016/j.celrep.2026.118110

Chenxu Zhu, Sylvie Manuse, Quentin Perrier, Subhasree Venkatasubramaniyan, Houssam Akherraz, Norbert Lodej, Cathy I Ramos, Meiling Zhang, Christophe Grangeasse, Agnieszka Razim, François Leulier, Renata C Matos

{"title":"Host-triggered prophage induction drives Lactiplantibacillus plantarum symbiosis through bacterial lysis.","authors":"Chenxu Zhu, Sylvie Manuse, Quentin Perrier, Subhasree Venkatasubramaniyan, Houssam Akherraz, Norbert Lodej, Cathy I Ramos, Meiling Zhang, Christophe Grangeasse, Agnieszka Razim, François Leulier, Renata C Matos","doi":"10.1016/j.celrep.2026.118110","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118110","url":null,"abstract":"The release of bacterial bioactive molecules across the gut barrier is a crucial yet poorly understood step in host-microbe communication. Here, we identify a phage-driven mechanism associated with this process in the beneficial symbiont Lactiplantibacillus plantarum NC8 (LpNC8). We show that a stress-responsive prophage, pp2, undergoes activation and triggers holin-lysin-mediated bacterial lysis, leading to the production of infectious phage particles and increased extracellular recovery of bacterial vesicles carrying lipoteichoic acids. In a model of nutritional symbiosis, pp2-dependent lysis is required for LpNC8 to promote juvenile growth in undernourished Drosophila melanogaster. Disruption of prophage-mediated lysis impairs vesicle recovery and host growth promotion. Furthermore, we demonstrate that the copper cell region of the Drosophila midgut acts as a physiological trigger of prophage induction. Together, our findings link host intestinal physiology to prophage activity and bacterial lysis, revealing phage-driven lysis as a mechanism contributing to beneficial bacterial-host interactions during nutritional stress.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118110"},"PeriodicalIF":7.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135042","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

Introgression catalyzing plumage evolution and speciation in an Asian songbird complex. 渗透催化亚洲鸣禽群羽毛进化和物种形成。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-08 DOI: 10.1016/j.celrep.2026.118108

Chuan Jiang, Wenwen Zhu, Per Alström, Yanchun Xu, Yang Zhou, Jiazheng Jin, Nassoro Mohamed, Yue Ma, Suying Bai, Yang Liu, Bo Li

{"title":"Introgression catalyzing plumage evolution and speciation in an Asian songbird complex.","authors":"Chuan Jiang, Wenwen Zhu, Per Alström, Yanchun Xu, Yang Zhou, Jiazheng Jin, Nassoro Mohamed, Yue Ma, Suying Bai, Yang Liu, Bo Li","doi":"10.1016/j.celrep.2026.118108","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118108","url":null,"abstract":"Hybridization and introgression can promote speciation and phenotypic diversity. We investigated genomic divergence between two closely related Asian songbirds, Naumann's Thrush (Turdus naumanni, Nau) and Dusky Thrush (T. eunomus, Eun), and their evolutionary relationship with the geographically adjacent Red-throated Thrush (T. ruficollis, Ruf). Utilizing a de novo chromosome-level genome and whole-genome resequencing data from 66 individuals, we characterized differentiation and introgression among the three species. Genomic divergence between Nau and Eun was restricted to a few genomic islands that overlap with regions introgressed into Nau from Ruf. Notably, these regions harbor three melanin-related genes under strong selection in Nau (ASIP, OCA2, and HERC2), which may account for the plumage similarity between Nau and Ruf. These findings suggest that the morphological and genetic divergence between Nau and Eun may have been driven by adaptive introgression of melanin-related genes from Ruf into Nau. This study reveals how introgression can generate rapid genomic and phenotypic divergence, indicating a potentially ubiquitous yet overlooked speciation mechanism.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118108"},"PeriodicalIF":7.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135045","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

A developmentally restricted γδ T cell-IL-17A axis supports mouse heart regeneration. 发育受限的γδ T细胞- il - 17a轴支持小鼠心脏再生。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-07 DOI: 10.1016/j.celrep.2026.118100

Stephanie Vargas Aguilar, Matthieu Dos Santos, Wei Tan, Efrain Sanchez-Ortiz, Kenian Chen, Hui Li, Lin Xu, Ning Liu, Eric N Olson

{"title":"A developmentally restricted γδ T cell-IL-17A axis supports mouse heart regeneration.","authors":"Stephanie Vargas Aguilar, Matthieu Dos Santos, Wei Tan, Efrain Sanchez-Ortiz, Kenian Chen, Hui Li, Lin Xu, Ning Liu, Eric N Olson","doi":"10.1016/j.celrep.2026.118100","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118100","url":null,"abstract":"Mammalian heart regeneration is restricted to a brief postnatal period during which neonatal-specific mechanisms, including a tightly regulated immune response, enable tissue repair. Here, we show that cardiac injury during the regenerative window induces the accumulation of a distinct γδ T cell population that is absent from older, non-regenerative hearts. Following injury, these cells serve as a rapid source of IL-17A, which shapes the timing and composition of the neonatal immune response. Genetic ablation of γδ T cells or disruption of IL-17 signaling limits heart regeneration and results in dysregulated immune cell infiltration and impaired cardiac function. Mechanistically, our data suggest that γδ T cell-derived IL-17A acts on myeloid cells to initiate a rapid, self-limited inflammatory response that facilitates apoptotic cell clearance and limits sustained inflammation. Our study identifies a developmentally restricted immune axis that supports heart regeneration and advances our understanding of how neonatal-specific immune circuits shape tissue repair.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118100"},"PeriodicalIF":7.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126697","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

Acute degron-mediated RUNX1 loss reprograms enhancer activity associated with epithelial destabilization and initiation of cancer hallmarks. 急性退化介导的RUNX1缺失重编程与上皮不稳定和癌症标志启动相关的增强子活性。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-07 DOI: 10.1016/j.celrep.2026.118101

Andrew J Fritz, Haley Greenyer, Louis Dillac, Priyanka Chavarkar, Akshay Neeli, Rahim Ullah, Miles Malik, Deli Hong, Rabail Toor, Emory Pacht, Abigail G Person, Georgiy Zotkin, Sadie Korzec, Cong Gao, Alquassem Abuorquob, Janine Warren, Jackson Del Porto, Jonah Perelman, Martin Montecino, Jane B Lian, Andre Van Wijnen, Jessica Heath, Prachi Ghule, Seth Frietze, Zaidi Sayyed, Kristy Stengel, Scott Hiebert, Kathleen Reed, Thomas Misteli, Jonathan A Gordon, Janet L Stein, Gary S Stein

{"title":"Acute degron-mediated RUNX1 loss reprograms enhancer activity associated with epithelial destabilization and initiation of cancer hallmarks.","authors":"Andrew J Fritz, Haley Greenyer, Louis Dillac, Priyanka Chavarkar, Akshay Neeli, Rahim Ullah, Miles Malik, Deli Hong, Rabail Toor, Emory Pacht, Abigail G Person, Georgiy Zotkin, Sadie Korzec, Cong Gao, Alquassem Abuorquob, Janine Warren, Jackson Del Porto, Jonah Perelman, Martin Montecino, Jane B Lian, Andre Van Wijnen, Jessica Heath, Prachi Ghule, Seth Frietze, Zaidi Sayyed, Kristy Stengel, Scott Hiebert, Kathleen Reed, Thomas Misteli, Jonathan A Gordon, Janet L Stein, Gary S Stein","doi":"10.1016/j.celrep.2026.118101","DOIUrl":"10.1016/j.celrep.2026.118101","url":null,"abstract":"RUNX1 coordinates phenotypic gene expression, and its suppression or perturbations are associated with breast tumor initiation and progression. Mechanisms governing the dual roles of RUNX1 in sustaining the mammary epithelial phenotype while suppressing initiation of cancer-compromised gene expression are unclear. Degron-mediated acute, selective, and complete RUNX1 ablation in human mammary epithelial cells reveals promoter and distal enhancer-driven expression of a gene cohort. RUNX1 ablation rapidly and selectively decreases chromatin accessibility and H3K27ac at RUNX1-bound enhancers but not promoters. While differentially initiated and expressed genes contacted by RUNX1-bound enhancers are enriched in epithelial maintenance and stemness pathways, genes with RUNX1-promoter occupancy support DNA damage responsiveness. Modified cell morphology, metabolic control, breast cancer stemness, plasticity, anchorage-independent survival, chemoresistance, and perturbed DNA damage reactivity are observed upon RUNX1 ablation. These findings define RUNX1 as a tumor suppressor maintaining epithelial cell state, preserving enhancer activity to prevent gene expression associated with cancer hallmarks.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118101"},"PeriodicalIF":7.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126719","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

HIF-1α-driven lactate from mesenchymal stem/stromal cells reprograms monocyte metabolism and suppresses autoimmune uveoretinitis. 间充质干细胞/基质细胞hif -1α驱动的乳酸重编程单核细胞代谢并抑制自身免疫性葡萄膜视网膜炎。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-07 DOI: 10.1016/j.celrep.2026.118104

Hyun Ju Lee, Jung Hwa Ko, Jin Suk Ryu, Joo Youn Oh

{"title":"HIF-1α-driven lactate from mesenchymal stem/stromal cells reprograms monocyte metabolism and suppresses autoimmune uveoretinitis.","authors":"Hyun Ju Lee, Jung Hwa Ko, Jin Suk Ryu, Joo Youn Oh","doi":"10.1016/j.celrep.2026.118104","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118104","url":null,"abstract":"Metabolic reprogramming of immune cells is emerging as a therapeutic strategy for autoimmune diseases. Here, we identify mesenchymal stem/stromal cell (MSC)-derived lactate as a signaling metabolite that reprograms monocyte metabolism and differentiation. GM-CSF enhanced glycolytic activity in bone marrow cells and expanded pro-inflammatory monocytes, whereas pharmacologic inhibition of glycolysis with 2-deoxy-D-glucose reversed these effects. MSC coculture suppressed glycolytic activation and redirected monocyte differentiation toward an immunosuppressive phenotype. MSCs produced lactate in a hypoxia-inducible factor 1α (HIF-1α)-dependent manner, and blocking lactate production through oxamate treatment or HIF1A knockdown attenuated the effects of MSCs on differentiating monocytes, whereas exogenous lactate recapitulated them. In experimental autoimmune uveoretinitis, intravenous administration of MSCs ameliorated the disease, but oxamate-pretreated or HIF1A-knockdown MSCs exhibited reduced efficacy. The HIF-1α-lactate axis may therefore represent a targetable pathway for optimizing MSC-based therapies and for developing lactate-centered interventions in autoimmune diseases.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118104"},"PeriodicalIF":7.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126687","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

Quantifying the energetic costs and growth benefits of phagocytosis. 量化吞噬的能量消耗和生长效益。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-07 DOI: 10.1016/j.celrep.2026.118105

Paul E Schavemaker, Kaitlyn S Tam, Michael Lynch

引用次数: 0

SNX17 facilitates entry and infection of Rift Valley fever virus and related bunyaviruses. SNX17促进裂谷热病毒和相关布尼亚病毒的进入和感染。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-07 DOI: 10.1016/j.celrep.2026.118082

Safder S Ganaie, Farheen Fatma, Zhengzheng Hu, Marco Grodzki, Rachael E Rush, Jennifer Clees, Griffin Brown, Olivia Barreca, Xiaoxia Cui, Byoung-Kyu Cho, Young Ah Goo, Amy L Hartman, Daisy W Leung, Gaya K Amarasinghe

{"title":"SNX17 facilitates entry and infection of Rift Valley fever virus and related bunyaviruses.","authors":"Safder S Ganaie, Farheen Fatma, Zhengzheng Hu, Marco Grodzki, Rachael E Rush, Jennifer Clees, Griffin Brown, Olivia Barreca, Xiaoxia Cui, Byoung-Kyu Cho, Young Ah Goo, Amy L Hartman, Daisy W Leung, Gaya K Amarasinghe","doi":"10.1016/j.celrep.2026.118082","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118082","url":null,"abstract":"Bunyaviruses are a group of multisegmented, negative-sense RNA viruses. Rift Valley fever virus (RVFV) is a representative member that can cause sporadic human outbreaks. We previously identified low-density lipoprotein receptor-related protein 1 (LRP1) as a host entry factor for RVFV and several bunyaviruses. This screen also identified additional factors as proviral host proteins, including sorting nexin 17 (SNX17). Here, we describe efforts to characterize SNX17 in bunyaviral infection. Our findings reveal that the removal of SNX17 results in a substantial reduction of RVFV infection in SNX17 knockout (KO) cells. Further analysis revealed that SNX17 removal resulted in a reduction but not complete elimination of LRP1 expression. Importantly, SNX17 interacts with full-length RVFV Gc and, upon infection by RVFV, co-migrates with RVFV to late endosomes. In addition to RVFV, several other bunyaviruses also appear to be dependent on SNX17 for infection, suggesting a potential broader role for SNX17 in bunyaviral entry.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118082"},"PeriodicalIF":7.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134990","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

Functional identification of non-coding regulatory regions that drive breast and skin carcinogenesis. 驱动乳腺癌和皮肤癌发生的非编码调控区域的功能鉴定。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-07 DOI: 10.1016/j.celrep.2026.118111

Robin H Oh, Kevin C L Cheng, Evgenija Serafimova, Ellen Langille, Miguel Ángel Pérez-Castro, Christopher Lowden, Jocelyn Nurtanto, Julien Dessapt, Iosifina Fotiadou, Shahan Haider, Jacob Berman, Ricky Tsai, Ahmad Malik, Liis Uusküla-Reimand, Sampath K Loganathan, Khalid N Al-Zahrani, Jüri Reimand, Daniel Schramek

{"title":"Functional identification of non-coding regulatory regions that drive breast and skin carcinogenesis.","authors":"Robin H Oh, Kevin C L Cheng, Evgenija Serafimova, Ellen Langille, Miguel Ángel Pérez-Castro, Christopher Lowden, Jocelyn Nurtanto, Julien Dessapt, Iosifina Fotiadou, Shahan Haider, Jacob Berman, Ricky Tsai, Ahmad Malik, Liis Uusküla-Reimand, Sampath K Loganathan, Khalid N Al-Zahrani, Jüri Reimand, Daniel Schramek","doi":"10.1016/j.celrep.2026.118111","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118111","url":null,"abstract":"Whole-genome sequencing has revealed hundreds of cancer driver mutations in protein-coding genes, while our knowledge of how non-coding mutations contribute to tumorigenesis remains limited. Here, we develop and perform large-scale functional screens to identify non-coding regulatory elements whose mutations drive cancer development in non-transformed human breast epithelial cells and mouse models of breast and skin cancer. We identify 12 frequently mutated regulatory elements associated with 16 genes as candidate cancer drivers. Mechanistically, we characterize two elements associated with the microRNA MIR21 and the tumor suppressor gene, ZFP36L2. Mutating these regulatory elements dysregulates the expression of MIR21 and ZFP36L2, thereby leading to oncogenic transformation. We identify ZFP36L2 as a p53 target gene and find that mutating the p53-binding motif in the ZFP36L2 promoter is sufficient to drive tumorigenesis. Conceptually, our data indicate that cancer driver mutations in non-coding regulatory elements are much more prevalent and potent than initially assumed.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118111"},"PeriodicalIF":7.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134946","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

Single-cell transcriptomics reveals the heterogeneous landscape of innate lymphoid cells in zebrafish. 单细胞转录组学揭示了斑马鱼先天淋巴样细胞的异质性景观。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-07 DOI: 10.1016/j.celrep.2026.118086

Kefan Cheng, Thi Huong Trinh, Ying Cao, Shachuan Feng, Jiaxin Liang, Shizheng Zhao, Jiaxu Yin, Tao Dong, Zilong Wen

{"title":"Single-cell transcriptomics reveals the heterogeneous landscape of innate lymphoid cells in zebrafish.","authors":"Kefan Cheng, Thi Huong Trinh, Ying Cao, Shachuan Feng, Jiaxin Liang, Shizheng Zhao, Jiaxu Yin, Tao Dong, Zilong Wen","doi":"10.1016/j.celrep.2026.118086","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118086","url":null,"abstract":"Innate lymphoid cells (ILCs) are a class of lymphocytes whose activation is independent of antigen receptors. Unlike mammals, where ILCs represent a small lymphoid subset, they are a dominant lymphocyte population in lower vertebrates and are thought to fulfill critical immunological roles in these animals. Yet their exact composition and functional activities remain largely uncharacterized. Here, using scRNA-seq, we identify a broad spectrum of distinct ILC subsets, including conventional subsets resembling their mammalian counterparts and unconventional ILC-like populations with unique features and distinct tissue distributions. We demonstrate that the complete ILC repertoire emerges early in development, independent of hematopoietic stem cells (HSCs), yet is maintained into adulthood via an HSC-dependent mechanism. Furthermore, we identify the essential role of interleukin-2 receptor beta (il2rβ) in zebrafish ILC-mediated immunity. Our work defines the landscape and ontogeny of zebrafish ILCs, revealing their underappreciated diversity and providing key insights into vertebrate innate immunity evolution.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118086"},"PeriodicalIF":7.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126785","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

Mitochondrial transfer protects against cisplatin-induced hearing loss by fumarate-mediated activation of mitophagy. 线粒体转移通过富马酸介导的线粒体自噬激活保护顺铂诱导的听力损失。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-07 DOI: 10.1016/j.celrep.2026.118107

Yunhao Wu, Yunhui Gu, Yukai Wang, Rui Li, Weiwei Shi, Jiaxin Liu, Changjie Lai, Xinyu Wang, Jie Tang, Donghui Pan, Yi Zhang, Ning Wei, Yiwen Zheng, Jing Wang, Min Yang, Xiaolong Fu, Renjie Chai, Guangji Wang, Yunlong Shan

{"title":"Mitochondrial transfer protects against cisplatin-induced hearing loss by fumarate-mediated activation of mitophagy.","authors":"Yunhao Wu, Yunhui Gu, Yukai Wang, Rui Li, Weiwei Shi, Jiaxin Liu, Changjie Lai, Xinyu Wang, Jie Tang, Donghui Pan, Yi Zhang, Ning Wei, Yiwen Zheng, Jing Wang, Min Yang, Xiaolong Fu, Renjie Chai, Guangji Wang, Yunlong Shan","doi":"10.1016/j.celrep.2026.118107","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118107","url":null,"abstract":"Sensorineural hearing loss (SNHL) affects millions of individuals worldwide, with platinum-based chemotherapeutics identified as a significant cause. In this study, we elucidate the mechanism by which mitochondrial transfer from mesenchymal stem/stromal cells (MSCs) protects against cisplatin-induced cochlear injury in a mouse model. Systemically administered MSCs home to the cochlea and transfer mitochondria to damaged spiral ganglion neurons (SGNs) via tunneling nanotubes, leading to elevated intracellular levels of the Krebs cycle intermediate fumarate, which activates mitophagy to eliminate dysfunctional mitochondria. Mechanistically, dimethyl fumarate (DMF)-a clinically available fumarate derivative-covalently modifies the phosphatase PPP1CB at cysteine 126, thereby blocking PPP1CB-mediated dephosphorylation of mitofusin 2 (MFN2), which in turn enhances mitophagy and ultimately preserves auditory function. These findings reveal that MSCs orchestrate mitochondrial replacement in damaged SGNs by delivering healthy mitochondria and facilitating the removal of impaired ones, underscoring the therapeutic potential of this strategy for treating SNHL related to mitochondrial dysfunction.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118107"},"PeriodicalIF":7.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126799","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