Cell Discovery最新文献_第9页

Author Correction: Ketogenic diet-produced β-hydroxybutyric acid accumulates brain GABA and increases GABA/glutamate ratio to inhibit epilepsy. 作者更正：生酮饮食产生的β-羟丁酸可积聚脑内GABA并增加GABA/谷氨酸比率，从而抑制癫痫。

IF 33.5 1区生物学

Cell Discovery Pub Date : 2024-04-30 DOI: 10.1038/s41421-024-00669-w

Ya-Nan Qiao, Lei Li, Song-Hua Hu, Yuan-Xin Yang, Zhen-Zhen Ma, Lin Huang, Yan-Peng An, Yi-Yuan Yuan, Yan Lin, Wei Xu, Yao Li, Peng-Cheng Lin, Jing Cao, Jian-Yuan Zhao, Shi-Min Zhao

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Treating a type 2 diabetic patient with impaired pancreatic islet function by personalized endoderm stem cell-derived islet tissue 通过个性化内胚层干细胞衍生胰岛组织治疗胰岛功能受损的 2 型糖尿病患者

IF 33.5 1区生物学

Cell Discovery Pub Date : 2024-04-30 DOI: 10.1038/s41421-024-00662-3

Jiaying Wu, Tuo Li, Meng Guo, Junsong Ji, Xiaoxi Meng, Tianlong Fu, Tengfei Nie, Tongkun Wei, Ying Zhou, Weihua Dong, Ming Zhang, Yongquan Shi, Xin Cheng, Hao Yin

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ANKFY1 bridges ATG2A-mediated lipid transfer from endosomes to phagophores ANKFY1 是 ATG2A 介导的脂质从内体转移到吞噬细胞的桥梁

IF 33.5 1区生物学

Cell Discovery Pub Date : 2024-04-16 DOI: 10.1038/s41421-024-00659-y

Bin Wei, Yuhui Fu, Xiuzhi Li, Fang Chen, Yiqing Zhang, Hanmo Chen, Mindan Tong, Linsen Li, Yi Pan, Shen Zhang, She Chen, Xiaoxia Liu, Qing Zhong

{"title":"ANKFY1 bridges ATG2A-mediated lipid transfer from endosomes to phagophores","authors":"Bin Wei, Yuhui Fu, Xiuzhi Li, Fang Chen, Yiqing Zhang, Hanmo Chen, Mindan Tong, Linsen Li, Yi Pan, Shen Zhang, She Chen, Xiaoxia Liu, Qing Zhong","doi":"10.1038/s41421-024-00659-y","DOIUrl":"https://doi.org/10.1038/s41421-024-00659-y","url":null,"abstract":"Macroautophagy is a process that cells engulf cytosolic materials by autophagosomes and deliver them to lysosomes for degradation. The biogenesis of autophagosomes requires ATG2 as a lipid transfer protein to transport lipids from existing membranes to phagophores. It is generally believed that endoplasmic reticulum is the main source for lipid supply of the forming autophagosomes; whether ATG2 can transfer lipids from other organelles to phagophores remains elusive. In this study, we identified a new ATG2A-binding protein, ANKFY1. Depletion of this endosome-localized protein led to the impaired autophagosome growth and the reduced autophagy flux, which largely phenocopied ATG2A/B depletion. A pool of ANKFY1 co-localized with ATG2A between endosomes and phagophores and depletion of UVRAG, ANKFY1 or ATG2A/B led to reduction of PI3P distribution on phagophores. Purified recombinant ANKFY1 bound to PI3P on membrane through its FYVE domain and enhanced ATG2A-mediated lipid transfer between PI3P-containing liposomes. Therefore, we propose that ANKFY1 recruits ATG2A to PI3P-enriched endosomes and promotes ATG2A-mediated lipid transfer from endosomes to phagophores. This finding implicates a new lipid source for ATG2A-mediated phagophore expansion, where endosomes donate PI3P and other lipids to phagophores via lipid transfer.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"28 1","pages":""},"PeriodicalIF":33.5,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140564504","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

Engineered, nucleocytoplasmic shuttling Cas13d enables highly efficient cytosolic RNA targeting 经过设计的核细胞质穿梭 Cas13d 可实现高效的细胞质 RNA 靶向

IF 33.5 1区生物学

Cell Discovery Pub Date : 2024-04-12 DOI: 10.1038/s41421-024-00672-1

Christoph Gruber, Lea Krautner, Valter Bergant, Vincent Grass, Zhe Ma, Lara Rheinemann, Ariane Krus, Friederike Reinhardt, Lyupka Mazneykova, Marianne Rocha-Hasler, Dong-Jiunn Jeffery Truong, Gil Gregor Westmeyer, Andreas Pichlmair, Gregor Ebert, Florian Giesert, Wolfgang Wurst

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Integration of 3D bioprinting and multi-algorithm machine learning identified glioma susceptibilities and microenvironment characteristics 三维生物打印与多算法机器学习的整合识别了胶质瘤的易感性和微环境特征

IF 33.5 1区生物学

Cell Discovery Pub Date : 2024-04-09 DOI: 10.1038/s41421-024-00650-7

Min Tang, Shan Jiang, Xiaoming Huang, Chunxia Ji, Yexin Gu, Ying Qi, Yi Xiang, Emmie Yao, Nancy Zhang, Emma Berman, Di Yu, Yunjia Qu, Longwei Liu, David Berry, Yu Yao

{"title":"Integration of 3D bioprinting and multi-algorithm machine learning identified glioma susceptibilities and microenvironment characteristics","authors":"Min Tang, Shan Jiang, Xiaoming Huang, Chunxia Ji, Yexin Gu, Ying Qi, Yi Xiang, Emmie Yao, Nancy Zhang, Emma Berman, Di Yu, Yunjia Qu, Longwei Liu, David Berry, Yu Yao","doi":"10.1038/s41421-024-00650-7","DOIUrl":"https://doi.org/10.1038/s41421-024-00650-7","url":null,"abstract":"Glioma, with its heterogeneous microenvironments and genetic subtypes, presents substantial challenges for treatment prediction and development. We integrated 3D bioprinting and multi-algorithm machine learning as a novel approach to enhance the assessment and understanding of glioma treatment responses and microenvironment characteristics. The bioprinted patient-derived glioma tissues successfully recapitulated molecular properties and drug responses of native tumors. We then developed GlioML, a machine learning workflow incorporating nine distinct algorithms and a weighted ensemble model that generated robust gene expression-based predictors, each reflecting the diverse action mechanisms of various compounds and drugs. The ensemble model superseded the performance of all individual algorithms across diverse in vitro systems, including sphere cultures, complex 3D bioprinted multicellular models, and 3D patient-derived tissues. By integrating bioprinting, the evaluative scope of the treatment expanded to T cell-related therapy and anti-angiogenesis targeted therapy. We identified promising compounds and drugs for glioma treatment and revealed distinct immunosuppressive or angiogenic myeloid-infiltrated tumor microenvironments. These insights pave the way for enhanced therapeutic development for glioma and potentially for other cancers, highlighting the broad application potential of this integrative and translational approach.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"73 1","pages":""},"PeriodicalIF":33.5,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140564686","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

Resistance mechanisms of SARS-CoV-2 3CLpro to the non-covalent inhibitor WU-04 SARS-CoV-2 3CLpro 对非共价抑制剂 WU-04 的抗药性机制

IF 33.5 1区生物学

Cell Discovery Pub Date : 2024-04-09 DOI: 10.1038/s41421-024-00673-0

Lijing Zhang, Xuping Xie, Hannan Luo, Runtong Qian, Yang Yang, Hongtao Yu, Jing Huang, Pei-Yong Shi, Qi Hu

{"title":"Resistance mechanisms of SARS-CoV-2 3CLpro to the non-covalent inhibitor WU-04","authors":"Lijing Zhang, Xuping Xie, Hannan Luo, Runtong Qian, Yang Yang, Hongtao Yu, Jing Huang, Pei-Yong Shi, Qi Hu","doi":"10.1038/s41421-024-00673-0","DOIUrl":"https://doi.org/10.1038/s41421-024-00673-0","url":null,"abstract":"Drug resistance poses a significant challenge in the development of effective therapies against SARS-CoV-2. Here, we identified two double mutations, M49K/M165V and M49K/S301P, in the 3C-like protease (3CLpro) that confer resistance to a novel non-covalent inhibitor, WU-04, which is currently in phase III clinical trials (NCT06197217). Crystallographic analysis indicates that the M49K mutation destabilizes the WU-04-binding pocket, impacting the binding of WU-04 more significantly than the binding of 3CLpro substrates. The M165V mutation directly interferes with WU-04 binding. The S301P mutation, which is far from the WU-04-binding pocket, indirectly affects WU-04 binding by restricting the rotation of 3CLpro’s C-terminal tail and impeding 3CLpro dimerization. We further explored 3CLpro mutations that confer resistance to two clinically used inhibitors: ensitrelvir and nirmatrelvir, and revealed a trade-off between the catalytic activity, thermostability, and drug resistance of 3CLpro. We found that mutations at the same residue (M49) can have distinct effects on the 3CLpro inhibitors, highlighting the importance of developing multiple antiviral agents with different skeletons for fighting SARS-CoV-2. These findings enhance our understanding of SARS-CoV-2 resistance mechanisms and inform the development of effective therapeutics.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"50 1","pages":""},"PeriodicalIF":33.5,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140564689","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

Immunological aspects of central neurodegeneration 中枢神经变性的免疫学问题

IF 33.5 1区生物学

Cell Discovery Pub Date : 2024-04-09 DOI: 10.1038/s41421-024-00666-z

Mireia Niso-Santano, José M. Fuentes, Lorenzo Galluzzi

引用次数: 0

Biogenesis of Rab14-positive endosome buds at Golgi–endosome contacts by the RhoBTB3–SHIP164–Vps26B complex RhoBTB3-SHIP164-Vps26B复合体在高尔基内质体接触处的Rab14阳性内质体芽的生物生成

IF 33.5 1区生物学

Cell Discovery Pub Date : 2024-04-02 DOI: 10.1038/s41421-024-00651-6

Jingru Wang, Juan Xiong, Shuhan Zhang, Dongchen Li, Qingzhu Chu, Weiping Chang, Lin Deng, Wei-Ke Ji

{"title":"Biogenesis of Rab14-positive endosome buds at Golgi–endosome contacts by the RhoBTB3–SHIP164–Vps26B complex","authors":"Jingru Wang, Juan Xiong, Shuhan Zhang, Dongchen Li, Qingzhu Chu, Weiping Chang, Lin Deng, Wei-Ke Ji","doi":"10.1038/s41421-024-00651-6","DOIUrl":"https://doi.org/10.1038/s41421-024-00651-6","url":null,"abstract":"Early endosomes (EEs) are crucial in cargo sorting within vesicular trafficking. While cargoes destined for degradation are retained in EEs and eventually transported to lysosomes, recycled cargoes for the plasma membrane (PM) or the Golgi undergo segregation into specialized membrane structures known as EE buds during cargo sorting. Despite this significance, the molecular basis of the membrane expansion during EE bud formation has been poorly understood. In this study, we identify a protein complex comprising SHIP164, an ATPase RhoBTB3, and a retromer subunit Vps26B, which promotes the formation of EE buds at Golgi–EE contacts. Our findings reveal that Vps26B acts as a novel Rab14 effector, and Rab14 activity regulates the association of SHIP164 with EEs. Depletion of SHIP164 leads to enlarged Rab14+ EEs without buds, a phenotype rescued by wild-type SHIP164 but not the lipid transfer-defective mutants. Suppression of RhoBTB3 or Vps26B mirrors the effects of SHIP164 depletion. Together, we propose a lipid transport-dependent pathway mediated by the RhoBTB3–SHIP164–Vps26B complex at Golgi–EE contacts, which is essential for EE budding.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"35 1","pages":""},"PeriodicalIF":33.5,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140564640","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

Structural basis for promiscuity in ligand recognition by yjdF riboswitch yjdF 核糖开关识别配体的结构基础

IF 33.5 1区生物学

Cell Discovery Pub Date : 2024-04-02 DOI: 10.1038/s41421-024-00663-2

Daniel Krochmal, Christina Roman, Anna Lewicka, Yaming Shao, Joseph A. Piccirilli

引用次数: 0

Microplastics dampen the self-renewal of hematopoietic stem cells by disrupting the gut microbiota-hypoxanthine-Wnt axis. 微塑料通过破坏肠道微生物群-次黄嘌呤-Wnt轴抑制造血干细胞的自我更新。

IF 33.5 1区生物学

Cell Discovery Pub Date : 2024-03-29 DOI: 10.1038/s41421-024-00665-0

Lingli Jiang, Yishan Ye, Yingli Han, Qiwei Wang, Huan Lu, Jinxin Li, Wenchang Qian, Xin Zeng, Zhaoru Zhang, Yanmin Zhao, Jimin Shi, Yi Luo, Yunfei Qiu, Jun Sun, Jinghao Sheng, He Huang, Pengxu Qian

{"title":"Microplastics dampen the self-renewal of hematopoietic stem cells by disrupting the gut microbiota-hypoxanthine-Wnt axis.","authors":"Lingli Jiang, Yishan Ye, Yingli Han, Qiwei Wang, Huan Lu, Jinxin Li, Wenchang Qian, Xin Zeng, Zhaoru Zhang, Yanmin Zhao, Jimin Shi, Yi Luo, Yunfei Qiu, Jun Sun, Jinghao Sheng, He Huang, Pengxu Qian","doi":"10.1038/s41421-024-00665-0","DOIUrl":"10.1038/s41421-024-00665-0","url":null,"abstract":"Microplastics (MPs) are contaminants ubiquitously found in the global biosphere that enter the body through inhalation or ingestion, posing significant risks to human health. Recent studies emerge that MPs are present in the bone marrow and damage the hematopoietic system. However, it remains largely elusive about the specific mechanisms by which MPs affect hematopoietic stem cells (HSCs) and their clinical relevance in HSC transplantation (HSCT). Here, we established a long-term MPs intake mouse model and found that MPs caused severe damage to the hematopoietic system. Oral gavage administration of MPs or fecal transplantation of microbiota from MPs-treated mice markedly undermined the self-renewal and reconstitution capacities of HSCs. Mechanistically, MPs did not directly kill HSCs but disrupted gut structure and permeability, which eventually ameliorated the abundance of Rikenellaceae and hypoxanthine in the intestine and inactivated the HPRT-Wnt signaling in bone marrow HSCs. Furthermore, administration of Rikenellaceae or hypoxanthine in mice as well as treatment of WNT10A in the culture system substantially rescued the MPs-induced HSC defects. Finally, we validated in a cohort of human patients receiving allogenic HSCT from healthy donors, and revealed that the survival time of patients was negatively correlated with levels of MPs, while positively with the abundance of Rikenellaceae, and hypoxanthine in the HSC donors' feces and blood. Overall, our study unleashes the detrimental roles and mechanisms of MPs in HSCs, which provides potential strategies to prevent hematopoietic damage from MPs and serves as a fundamental critique for selecting suitable donors for HSCT in clinical practice.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"10 1","pages":"35"},"PeriodicalIF":33.5,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10978833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140317854","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