Cell Research最新文献_第2页

White matter interactome in vascular dementia. 血管性痴呆的白质相互作用。

IF 44.1 1区生物学

Cell Research Pub Date : 2025-09-17 DOI: 10.1038/s41422-025-01175-8

Stefan Wendt,Brian A MacVicar

引用次数: 0

Deconstructing the architecture of memory engrams. 解构记忆印迹的架构。

IF 44.1 1区生物学

Cell Research Pub Date : 2025-09-17 DOI: 10.1038/s41422-025-01179-4

Yi Zhong,Bo Lei

引用次数: 0

Soluble tissue factor generated by necroptosis-triggered shedding is responsible for thrombosis 坏死引发的脱落所产生的可溶性组织因子是导致血栓形成的原因

IF 44.1 1区生物学

Cell Research Pub Date : 2025-09-12 DOI: 10.1038/s41422-025-01167-8

Peixing Wan, Swati Choksi, Yeon-Ji Park, Xin Chen, Jiong Yan, Sahar Foroutannejad, Zhaoshan Liu, Jichun Chen, Ross Lake, Chengyu Liu, Zheng-Gang Liu

{"title":"Soluble tissue factor generated by necroptosis-triggered shedding is responsible for thrombosis","authors":"Peixing Wan, Swati Choksi, Yeon-Ji Park, Xin Chen, Jiong Yan, Sahar Foroutannejad, Zhaoshan Liu, Jichun Chen, Ross Lake, Chengyu Liu, Zheng-Gang Liu","doi":"10.1038/s41422-025-01167-8","DOIUrl":"https://doi.org/10.1038/s41422-025-01167-8","url":null,"abstract":"Tissue factor (TF) is a cell surface protein critical for normal hemostasis and pathological thrombosis. Necroptosis is a form of regulated necrosis associated with different diseases. Here, we reported the identification of the first functional soluble tissue factor (sTF) in mediating blood coagulation, shed from the membrane full-length TF (flTF) by proteases, ADAMs, during necroptosis. By generating sTF-specific antibody and transgenic mice carrying knockin mutations at the ADAM cleavage site of TF (T211V212 mutated to E211E212), we demonstrated that this sTF is responsible for necroptosis-related thrombosis in inflammation and viral infection mouse models. Importantly, we showed that eliminating necroptosis or the cleavage of the flTF blocked the production of sTF and prevented thrombosis in mice. We also detected sTF in the plasma of human COVID-19 patients and showed that SARS-CoV-2 pseudovirus induced sTF production. Our findings demonstrated that the sTF plays a major role in thrombosis under necroptosis-related pathological conditions and provided a diagnostic marker and potential therapies for treating thrombosis without affecting hemostasis.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"67 1","pages":""},"PeriodicalIF":44.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145035310","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

An anti-inflammatory autophagic target in chronic diseases 慢性疾病中的抗炎自噬靶点

IF 44.1 1区生物学

Cell Research Pub Date : 2025-09-11 DOI: 10.1038/s41422-025-01176-7

Prithvi Reddy Akepati, Vojo Deretic

引用次数: 0

APOL proteins tune gut immunity via commensal lipid recognition APOL蛋白通过共生脂质识别调节肠道免疫

IF 44.1 1区生物学

Cell Research Pub Date : 2025-09-08 DOI: 10.1038/s41422-025-01166-9

Shohei Asami, Hiroshi Ohno

引用次数: 0

Molecular characterization of endosomal self RNA Rmrp-engaged TLR3 dimerization to prime innate activation. 内体自身RNA rmrp参与TLR3二聚化以启动先天激活的分子特征。

IF 44.1 1区生物学

Cell Research Pub Date : 2025-09-08 DOI: 10.1038/s41422-025-01178-5

Shikun Zhang,Bo Li,Lun Liu,Dongsheng Gong,Deyu Zhang,Fengjiang Liu,Xiuna Yang,Hua Qin,Deling Kong,Shuyang Zhang,Zihe Rao,Xuetao Cao

{"title":"Molecular characterization of endosomal self RNA Rmrp-engaged TLR3 dimerization to prime innate activation.","authors":"Shikun Zhang,Bo Li,Lun Liu,Dongsheng Gong,Deyu Zhang,Fengjiang Liu,Xiuna Yang,Hua Qin,Deling Kong,Shuyang Zhang,Zihe Rao,Xuetao Cao","doi":"10.1038/s41422-025-01178-5","DOIUrl":"https://doi.org/10.1038/s41422-025-01178-5","url":null,"abstract":"The pre-dimerization of endosome-localized RNA sensor Toll-like receptor 3 (TLR3) is required for its innate recognition, yet how TLR3 pre-dimers are formed and precisely primed for innate activation remains unclear. Here, we demonstrate that endosome-localized self RNA Rmrp directly binds to TLR3 and induces TLR3 dimerization in the early endosome but does not interact with endosome-localized TLR7, TLR8, TLR9 or cytoplasmic RNA sensor RIG-I under homeostatic conditions. Cryo-EM structure of Rmrp-TLR3 complex reveals a novel lapped conformation of TLR3 dimer engaged by Rmrp, which is distinct from the activation mechanism by dsRNA and the specific structural feature at the 3'-end of Rmrp is critical for its functional interaction with TLR3. Furthermore, K42 residue of TLR3 is essential for binding to Rmrp and subsequent dimerization. Rmrp dissociates from TLR3 following endosomal acidification, generating a matured TLR3 dimer which is primed for innate recognition and activation. Myeloid-cell deficiency of Rmrp reduces TLR3 dimerization and attenuates TLR3-mediated antiviral responses against influenza A both in vitro and in vivo. These findings elucidate the structural mode of self RNA Rmrp-primed TLR3 dimerization and ready for efficient innate recognition on endosomal membrane, extending our knowledge of how membrane-associated TLRs pre-dimerize and suggesting a new function of subcellular localized self RNAs in empowering innate activation.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"11 1","pages":""},"PeriodicalIF":44.1,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008738","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

Osteocalcin has many tricks to get γ-carboxylated 骨钙素有很多方法来使γ-羧化

IF 25.9 1区生物学

Cell Research Pub Date : 2025-09-05 DOI: 10.1038/s41422-025-01177-6

Mathieu Ferron

引用次数: 0

Targeting necrotic lipid release in tumors enhances immunosurveillance and cancer immunotherapy of glioblastoma 靶向肿瘤坏死脂质释放增强胶质母细胞瘤的免疫监测和肿瘤免疫治疗

IF 44.1 1区生物学

Cell Research Pub Date : 2025-09-03 DOI: 10.1038/s41422-025-01155-y

Yapeng Ji, Junyao Jiang, Lei Hu, Peng Lin, Mingshan Zhou, Song Hu, Minkai Wang, Yuchen Ji, Xianzhi Liu, Dongming Yan, Yang Guo, Adwait Amod Sathe, Bret M. Evers, Chao Xing, Xuelian Luo, Qi Xie, Weike Pei, Zhenyu Zhang, Hongtao Yu

{"title":"Targeting necrotic lipid release in tumors enhances immunosurveillance and cancer immunotherapy of glioblastoma","authors":"Yapeng Ji, Junyao Jiang, Lei Hu, Peng Lin, Mingshan Zhou, Song Hu, Minkai Wang, Yuchen Ji, Xianzhi Liu, Dongming Yan, Yang Guo, Adwait Amod Sathe, Bret M. Evers, Chao Xing, Xuelian Luo, Qi Xie, Weike Pei, Zhenyu Zhang, Hongtao Yu","doi":"10.1038/s41422-025-01155-y","DOIUrl":"https://doi.org/10.1038/s41422-025-01155-y","url":null,"abstract":"Tumors evolve to avoid immune destruction and establish an immunosuppressive microenvironment. Syngeneic mouse tumor models are critical for understanding tumor immune evasion and testing cancer immunotherapy. Derived from established mouse tumor cell lines that can already evade the immune system, these models cannot simulate early phases of immunoediting during initial tumorigenesis. We developed a syngeneic mouse teratoma model derived from noncancerous mouse embryonic stem cells and conducted a genome-wide CRISPR screen to identify genes that impact early phases of cancer immunoediting. We found that loss of pro-apoptotic tumor suppressor genes, including Trp53, increased necrosis in teratomas, releasing APOE lipid particles into the extracellular milieu. Infiltrating T cells drawn to tumor necrotic regions accumulated lipids and became dysfunctional. Blocking lipid uptake in T cells or reducing necrosis in teratomas by inactivating the mitochondrial permeability transition pore (mPTP) restored immunosurveillance. Because mouse teratomas were highly enriched for brain tissues, we next examined the tumor-immune interaction in human glioblastoma (GBM). Indeed, infiltrating T cells in TP53-mutated human GBM accumulated APOE and were dysfunctional. Anti-APOE and anti-PDCD1 antibodies synergistically boosted anti-GBM immunity and prolonged survival in mice. Our results link mPTP-mediated tumor necrosis to immune evasion and suggest that targeting the uptake of lipids released by necrotic tumor cells by infiltrating immune cells can enhance cancer immunotherapy.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"2 1","pages":""},"PeriodicalIF":44.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144930208","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

IF 25.9 1区生物学

Cell Research Pub Date : 2025-09-02 DOI: 10.1038/s41422-025-01174-9

Yisheng Jiang, Feipeng Zhu, Jie Zhong, Xiaomei Sun, Yuting Yuan, Shuo Wang, Haiyang Chen, Zhiheng Xu

{"title":"Autism-related proteins form a complex to maintain the striatal asymmetry in mice","authors":"Yisheng Jiang, Feipeng Zhu, Jie Zhong, Xiaomei Sun, Yuting Yuan, Shuo Wang, Haiyang Chen, Zhiheng Xu","doi":"10.1038/s41422-025-01174-9","DOIUrl":"10.1038/s41422-025-01174-9","url":null,"abstract":"The brain’s hemispheres exhibit profound lateralization, yet the underlying mechanisms remain elusive. Using proteomic and phosphoproteomic analyses of the bilateral striatum — a hub for important brain functions and a common node of autism pathophysiology — we identified significant phosphorylation asymmetries. Particularly, the phosphorylation processes in the left striatum appear more prone to disturbance. Notably, SH3RF2, whose single-copy knockout leads to autism spectrum disorder (ASD)-like behaviors in mice, is uniquely expressed in the striatum, forming a complex with CaMKII (an ASD-associated protein) and PPP1CC. Loss of SH3RF2 disturbs the CaMKII/PP1 “switch”, resulting in hyperactivity of CaMKII and increased phosphorylation of its substrate GluR1. In Sh3rf2-deficient mice, heightened GluR1-Ser831 phosphorylation and its aberrant postsynaptic membrane localization in the left striatum may impair the functional lateralization of striatal neurons and contribute to autism-like behaviors. This study unveils the first molecular mechanism governing brain lateralization in mammals, linking its impairment to autism development and treatment strategies.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 10","pages":"762-774"},"PeriodicalIF":25.9,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41422-025-01174-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144928211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural insights into the vitamin K-dependent γ-carboxylation of osteocalcin 对维生素k依赖性骨钙素γ-羧化的结构见解

IF 25.9 1区生物学

Cell Research Pub Date : 2025-09-02 DOI: 10.1038/s41422-025-01161-0

Qing Cao, Jianjun Fan, Aaron Ammerman, Samjhana Awasthi, Zongtao Lin, Saimi Mierxiati, Huaping Chen, Jinbin Xu, Benjamin A. Garcia, Bin Liu, Weikai Li

{"title":"Structural insights into the vitamin K-dependent γ-carboxylation of osteocalcin","authors":"Qing Cao, Jianjun Fan, Aaron Ammerman, Samjhana Awasthi, Zongtao Lin, Saimi Mierxiati, Huaping Chen, Jinbin Xu, Benjamin A. Garcia, Bin Liu, Weikai Li","doi":"10.1038/s41422-025-01161-0","DOIUrl":"10.1038/s41422-025-01161-0","url":null,"abstract":"The γ-carboxylation state of osteocalcin determines its essential functions in bone mineralization or systemic metabolism and serves as a prominent biomarker for bone health and vitamin K nutrition. This post-translational modification of glutamate residues is catalyzed by the membrane-embedded vitamin K-dependent γ-carboxylase (VKGC), which typically recognizes protein substrates through their tightly bound propeptide that triggers γ-carboxylation. However, the osteocalcin propeptide exhibits negligible affinity for VKGC. To understand the underlying molecular mechanism, we determined the cryo-electron microscopy structures of VKGC with osteocalcin carrying a native propeptide or a high-affinity variant at different carboxylation states. The structures reveal a large chamber in VKGC that maintains uncarboxylated and partially carboxylated osteocalcin in partially unfolded conformations, allowing their glutamate-rich region and C-terminal helices to engage with VKGC at multiple sites. Binding of this mature region together with the low-affinity propeptide effectively stimulates VKGC activity, similar to high-affinity propeptides that differ only in closely fitting interactions. However, the low-affinity propeptide renders osteocalcin prone to undercarboxylation at low vitamin K levels, thereby serving as a discernible biomarker. Overall, our studies reveal the unique interaction of osteocalcin with VKGC and provide a framework for designing therapeutic strategies targeting osteocalcin-related bone and metabolic disorders.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 10","pages":"735-749"},"PeriodicalIF":25.9,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144928541","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