Cell reportsPub Date : 2025-03-25DOI: 10.1016/j.celrep.2025.115463
Naokazu Inoue, Takako Saito, Ikuo Wada
{"title":"Noncanonical phagocytosis-like SEAL establishes mammalian fertilization.","authors":"Naokazu Inoue, Takako Saito, Ikuo Wada","doi":"10.1016/j.celrep.2025.115463","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115463","url":null,"abstract":"<p><p>In many forms of sexual reproduction, only the most robust spermatozoa, which overcome multiple physiological challenges, reach the oocyte. However, the exact mechanisms of gamete recognition and fusion are unknown. In the present study, we demonstrated that with the onset of gamete recognition, oocyte microvilli form lamellipodium-like structures, activate actin polymerization, and subsequently engulf spermatozoa to initiate gamete fusion. Gamete fusion occurred via a phagocytosis-like process we termed \"sperm engulfment activated by IZUMO1-JUNO linkage and gamete fusion-related factors\" (SEAL). Gamete adhesion was strictly regulated by binding of sperm IZUMO1 to oocyte JUNO, while SEAL was primarily mediated by sperm DCST1/2, SPACA6, TMEM95, FIMP, and TMEM81, the essential factors for gamete fusion. Interestingly, JUNO was almost depleted from oocyte surfaces in the region where SEAL enveloped spermatozoa by microvilli without actin polymerization. SEAL formation was recapitulated using JUNO-expressing K562 lymphocytic cells rather than oocytes. Together, these findings suggest that dynamic rearrangement of membrane components facilitates SEAL prior to successful fertilization.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 4","pages":"115463"},"PeriodicalIF":7.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728980","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}
Cell reportsPub Date : 2025-03-25Epub Date: 2025-02-20DOI: 10.1016/j.celrep.2025.115345
Yixuan Feng, Yiming Wang, Tai Wang, Lingtong Liu
{"title":"NUCLEAR RNA POLYMERASE D1 is essential for tomato embryogenesis and desiccation tolerance in seeds.","authors":"Yixuan Feng, Yiming Wang, Tai Wang, Lingtong Liu","doi":"10.1016/j.celrep.2025.115345","DOIUrl":"10.1016/j.celrep.2025.115345","url":null,"abstract":"<p><p>Plant-unique RNA polymerase IV (RNA Pol IV) governs the establishment of small RNA (sRNA)-directed DNA methylation (RdDM). In dicotyledon, elevated RdDM activity is often associated with embryogenesis; however, the loss of RdDM frequently results in indiscernible phenotypes. Here, we report that the absence of SlNRPD1, encoding the largest subunit of RNA Pol IV, leads to diminished RdDM and abnormal embryogenesis in tomato (Solanum lycopersicum). Hypermethylation at pericentric transposable elements (TEs) and a burst of 21/22-nt siRNA from the distal and pericentric genes are observed in slnrpd1 embryos. The specific activation of endoribonuclease Dicer-like 2 (SlDCL2b/c/d) is correlated with 21/22-nt sRNA accumulation. Auxin and WUSCHEL-related homeobox (WOX) signaling gene expression is altered by mCHH hypomethylation, which may lead to defective embryos. Due to improper maturation, the slnrpd1 embryos cannot withstand post-harvest desiccation. This study provides insights into how DNA methylation regulates plant embryogenesis.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 3","pages":"115345"},"PeriodicalIF":7.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472331","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}
Cell reportsPub Date : 2025-03-25Epub Date: 2025-02-25DOI: 10.1016/j.celrep.2025.115350
Jinyang Li, Xiancheng Chen, Shiyu Song, Wangjie Jiang, Tianjiao Geng, Tiantian Wang, Yan Xu, Yongqiang Zhu, Jun Lu, Yongxiang Xia, Rong Wang
{"title":"Hexokinase 2-mediated metabolic stress and inflammation burden of liver macrophages via histone lactylation in MASLD.","authors":"Jinyang Li, Xiancheng Chen, Shiyu Song, Wangjie Jiang, Tianjiao Geng, Tiantian Wang, Yan Xu, Yongqiang Zhu, Jun Lu, Yongxiang Xia, Rong Wang","doi":"10.1016/j.celrep.2025.115350","DOIUrl":"10.1016/j.celrep.2025.115350","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by metabolic dysfunction and inflammation burden, involving a significant enhancement of cellular glycolytic activity. Here, we elucidate how a positive feedback loop in liver macrophages drives MASLD pathogenesis and demonstrate that disrupting this cycle mitigates metabolic stress and macrophage M1 activation during MASLD. We detect elevated expression of hexokinase 2 (HK2) and H3K18la in liver macrophages from patients with MASLD and MASLD mice. This lactate-dependent histone lactylation promotes glycolysis and liver macrophage M1 polarization by enriching the promoters of glycolytic genes and activating transcription. Ultimately, the HK2/glycolysis/H3K18la positive feedback loop exacerbates the vicious cycle of enhancing metabolic dysregulation and histone lactylation and the inflammatory phenotype of liver macrophages. Myeloid-specific deletion of Hk2 or pharmacological inhibition of the transcription factor HIF-1α significantly disrupts this deleterious cycle. Therefore, our study illustrates that targeting this amplified pathogenic loop may offer a promising therapeutic strategy for MASLD.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 3","pages":"115350"},"PeriodicalIF":7.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522678","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":"The balance between IFN-γ and ERK/MAPK signaling activities ensures lifelong maintenance of intestinal stem cells.","authors":"May Nakajima-Koyama, Mio Kabata, Joonseong Lee, Yuko Sogabe, Satoko Sakurai, Akira Hirota, Mizuki Kimura, Tomonori Nakamura, Yusuke Imoto, Kohei Kometani, Yoko Hamazaki, Yasuaki Hiraoka, Mitinori Saitou, Eisuke Nishida, Takuya Yamamoto","doi":"10.1016/j.celrep.2025.115286","DOIUrl":"10.1016/j.celrep.2025.115286","url":null,"abstract":"<p><p>While the intestinal epithelium has the highest cellular turnover rates in the mammalian body, it is also considered one of the tissues most resilient to aging-related disorders. Here, we reveal an innate protective mechanism that safeguards intestinal stem cells (ISCs) from environmental conditions in the aged intestine. Using in vivo phenotypic analysis, transcriptomics, and in vitro intestinal organoid studies, we show that age-dependent activation of interferon-γ (IFN-γ) signaling and inactivation of extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling are responsible for establishing an equilibrium of Lgr5<sup>+</sup> ISCs-between active and quiescent states-to preserve the ISC pool during aging. Furthermore, we show that differentiated cells have different sensitivities to each of the two signaling pathways, which may induce aging-related, functional, and metabolic changes in the body. Thus, our findings reveal an exquisitely balanced, age-dependent signaling mechanism that preserves stem cells at the expense of differentiated cells.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":" ","pages":"115286"},"PeriodicalIF":7.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425014","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}
Cell reportsPub Date : 2025-03-25Epub Date: 2025-03-01DOI: 10.1016/j.celrep.2025.115358
Pau Pérez Escriva, Catarina Correia Tavares Bernardino, Elisabeth Letellier
{"title":"De-coding the complex role of microbial metabolites in cancer.","authors":"Pau Pérez Escriva, Catarina Correia Tavares Bernardino, Elisabeth Letellier","doi":"10.1016/j.celrep.2025.115358","DOIUrl":"10.1016/j.celrep.2025.115358","url":null,"abstract":"<p><p>The human microbiome, an intricate ecosystem of trillions of microbes residing across various body sites, significantly influences cancer, a leading cause of morbidity and mortality worldwide. Recent studies have illuminated the microbiome's pivotal role in cancer development, either through direct cellular interactions or by secreting bioactive compounds such as metabolites. Microbial metabolites contribute to cancer initiation through mechanisms such as DNA damage, epithelial barrier dysfunction, and chronic inflammation. Furthermore, microbial metabolites exert dual roles on cancer progression and response to therapy by modulating cellular metabolism, gene expression, and signaling pathways. Understanding these complex interactions is vital for devising new therapeutic strategies. This review highlights microbial metabolites as promising targets for cancer prevention and treatment, emphasizing their impact on therapy responses and underscoring the need for further research into their roles in metastasis and therapy resistance.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 3","pages":"115358"},"PeriodicalIF":7.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536645","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}
Cell reportsPub Date : 2025-03-25Epub Date: 2025-02-27DOI: 10.1016/j.celrep.2025.115376
Qiumin Feng, Zejin Lin, Danhui Zhao, Mengzhao Li, Sheng Yang, Andy Peng Xiang, Congting Ye, Chengguo Yao
{"title":"Functional inhibition of core spliceosomal machinery activates intronic premature cleavage and polyadenylation of pre-mRNAs.","authors":"Qiumin Feng, Zejin Lin, Danhui Zhao, Mengzhao Li, Sheng Yang, Andy Peng Xiang, Congting Ye, Chengguo Yao","doi":"10.1016/j.celrep.2025.115376","DOIUrl":"10.1016/j.celrep.2025.115376","url":null,"abstract":"<p><p>The catalytic role of U6 snRNP in pre-mRNA splicing has been well established. In this study, we utilize an antisense morpholino oligonucleotide (AMO) specifically targeting catalytic sites of U6 snRNA to achieve functional knockdown of U6 snRNP in HeLa cells. The data show a significant increase in global intronic premature cleavage and polyadenylation (PCPA) events, similar to those observed with U1 AMO treatment, as demonstrated by mRNA 3'-seq analysis. Mechanistically, we provide evidence that U6 AMO-mediated splicing inhibition might be the driving force for PCPA as application of another specific AMO targeting U2 snRNP results in similar global PCPA effects. Together with our recently published findings that demonstrate the global inhibitory effect of U4 snRNP on intronic PCPA, our data highlight the critical role of splicing in suppressing intronic PCPA and support a model in which splicing and polyadenylation may compete with each other within introns during co-transcriptional mRNA processing.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 3","pages":"115376"},"PeriodicalIF":7.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527928","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}
Cell reportsPub Date : 2025-03-25Epub Date: 2025-02-20DOI: 10.1016/j.celrep.2025.115344
Philip Hasel, Melissa L Cooper, Anne E Marchildon, Uriel Rufen-Blanchette, Rachel D Kim, Thong C Ma, Adam M R Groh, Emily J Hill, Eleanor M Lewis, Michał Januszewski, Sarah E W Light, Cody J Smith, Jo Anne Stratton, Steven A Sloan, Un Jung Kang, Moses V Chao, Shane A Liddelow
{"title":"Defining the molecular identity and morphology of glia limitans superficialis astrocytes in vertebrates.","authors":"Philip Hasel, Melissa L Cooper, Anne E Marchildon, Uriel Rufen-Blanchette, Rachel D Kim, Thong C Ma, Adam M R Groh, Emily J Hill, Eleanor M Lewis, Michał Januszewski, Sarah E W Light, Cody J Smith, Jo Anne Stratton, Steven A Sloan, Un Jung Kang, Moses V Chao, Shane A Liddelow","doi":"10.1016/j.celrep.2025.115344","DOIUrl":"10.1016/j.celrep.2025.115344","url":null,"abstract":"<p><p>Astrocytes are a highly abundant glial cell type and perform critical homeostatic functions in the central nervous system. Like neurons, astrocytes have many discrete heterogeneous subtypes. The subtype identity and functions are, at least in part, associated with their anatomical location and can be highly restricted to strategically important anatomical domains. Here, we report that astrocytes forming the glia limitans superficialis, the outermost border of the brain and spinal cord, are a highly specialized astrocyte subtype and can be identified by a single marker: myocilin (Myoc). We show that glia limitans superficialis astrocytes cover the entire brain and spinal cord surface, exhibit an atypical morphology, and are evolutionarily conserved from zebrafish, rodents, and non-human primates to humans. Identification of this highly specialized astrocyte subtype will advance our understanding of CNS homeostasis and potentially be targeted for therapeutic intervention to combat peripheral inflammatory effects on the CNS.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 3","pages":"115344"},"PeriodicalIF":7.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472327","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}
Cell reportsPub Date : 2025-03-25Epub Date: 2025-03-01DOI: 10.1016/j.celrep.2025.115364
Yuqing Wu, Lei Zhu, Sheng Li, Lu Liu, Yaman Wang, Yongbing Yang, Yuan Mu, Qiuying Zhu, Yuying Jiang, Chunyan Wu, Peiwen Xi, Chunmei Ma, Lijun Liang, Min Gao, Yingchao Hu, Qiang Ding, Shiyang Pan
{"title":"DA-DRD5 signaling reprograms B cells to promote CD8<sup>+</sup> T cell-mediated antitumor immunity.","authors":"Yuqing Wu, Lei Zhu, Sheng Li, Lu Liu, Yaman Wang, Yongbing Yang, Yuan Mu, Qiuying Zhu, Yuying Jiang, Chunyan Wu, Peiwen Xi, Chunmei Ma, Lijun Liang, Min Gao, Yingchao Hu, Qiang Ding, Shiyang Pan","doi":"10.1016/j.celrep.2025.115364","DOIUrl":"10.1016/j.celrep.2025.115364","url":null,"abstract":"<p><p>Neuronal signals have emerged as pivotal regulators of B cells that regulate antitumor immunity and tumor progression. However, the functional relevance and mechanistic basis of the effects of the neurotransmitter dopamine (DA) on tumor immunity remain elusive. Here, we discovered that plasma DA levels are positively correlated with circulating B cell numbers and potently activate B cell responses in a manner dependent on the DRD5 receptor. Notably, DRD5 signaling enhanced the Janus kinase 1 (JAK1)-STAT1 signaling in B cell responses, which enhanced B cell activation and increased antigen presentation and co-stimulation, resulting in increased expansion and cytotoxicity in tumor-specific effector of T cells. Our findings demonstrate that DA signaling suppresses tumor progression and highlight DRD5 as a promising target for cancer immunotherapy.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 3","pages":"115364"},"PeriodicalIF":7.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536716","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}
Cell reportsPub Date : 2025-03-25Epub Date: 2025-02-28DOI: 10.1016/j.celrep.2025.115371
Pierce W Ford, Danielle M Garshott, Mythreyi Narasimhan, Xuezhen Ge, Eric M Jordahl, Shubha Subramanya, Eric J Bennett
{"title":"RNF10 and RIOK3 facilitate 40S ribosomal subunit degradation upon 60S biogenesis disruption or amino acid starvation.","authors":"Pierce W Ford, Danielle M Garshott, Mythreyi Narasimhan, Xuezhen Ge, Eric M Jordahl, Shubha Subramanya, Eric J Bennett","doi":"10.1016/j.celrep.2025.115371","DOIUrl":"10.1016/j.celrep.2025.115371","url":null,"abstract":"<p><p>The initiation-specific ribosome-associated quality control pathway (iRQC) is activated when translation initiation complexes fail to transition to elongation-competent 80S ribosomes. Upon iRQC activation, RNF10 ubiquitylates the 40S proteins uS3 and uS5, which leads to 40S decay. How iRQC is activated in the absence of pharmacological translation inhibitors and what mechanisms govern iRQC capacity and activity remain unanswered questions. Here, we demonstrate that altering 60S:40S stoichiometry by disrupting 60S biogenesis triggers iRQC activation and 40S decay. Depleting the critical scanning helicase eIF4A1 impairs 40S ubiquitylation and degradation, indicating mRNA engagement is required for iRQC. We show that amino acid starvation conditions also stimulate iRQC-dependent 40S decay. We identify RIOK3 as a crucial iRQC factor that interacts with ubiquitylated 40S subunits to mediate degradation. Both RNF10 and RIOK3 protein levels increase upon iRQC pathway activation, establishing a feedforward mechanism that regulates iRQC capacity and subsequent 40S decay.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 3","pages":"115371"},"PeriodicalIF":7.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536758","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}
Cell reportsPub Date : 2025-03-25Epub Date: 2025-03-08DOI: 10.1016/j.celrep.2025.115455
Huiyuan Zhang, Asaf Madi, Nir Yosef, Norio Chihara, Amit Awasthi, Caroline Pot, Conner Lambden, Amitabh Srivastava, Patrick R Burkett, Jackson Nyman, Elena Christian, Yasaman Etminan, Annika Lee, Helene Stroh, Junrong Xia, Katarzyna Karwacz, Pratiksha I Thakore, Nandini Acharya, Alexandra Schnell, Chao Wang, Lionel Apetoh, Orit Rozenblatt-Rosen, Ana C Anderson, Aviv Regev, Vijay K Kuchroo
{"title":"An IL-27-Driven Transcriptional Network Identifies Regulators of IL-10 Expression across T Helper Cell Subsets.","authors":"Huiyuan Zhang, Asaf Madi, Nir Yosef, Norio Chihara, Amit Awasthi, Caroline Pot, Conner Lambden, Amitabh Srivastava, Patrick R Burkett, Jackson Nyman, Elena Christian, Yasaman Etminan, Annika Lee, Helene Stroh, Junrong Xia, Katarzyna Karwacz, Pratiksha I Thakore, Nandini Acharya, Alexandra Schnell, Chao Wang, Lionel Apetoh, Orit Rozenblatt-Rosen, Ana C Anderson, Aviv Regev, Vijay K Kuchroo","doi":"10.1016/j.celrep.2025.115455","DOIUrl":"10.1016/j.celrep.2025.115455","url":null,"abstract":"","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 3","pages":"115455"},"PeriodicalIF":7.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584922","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}