{"title":"SETD3-mediated histidine methylation of MCM7 regulates DNA replication by facilitating chromatin loading of MCM.","authors":"Hongguo Duan, Shuang Wang, Wen-Jie Shu, Yongjia Tong, Hai-Zhen Long, Guohong Li, Hai-Ning Du, Meng-Jie Zhao","doi":"10.1007/s11427-023-2600-0","DOIUrl":"10.1007/s11427-023-2600-0","url":null,"abstract":"<p><p>The minichromosome maintenance complex (MCM) DNA helicase is an important replicative factor during DNA replication. The proper chromatin loading of MCM is a key step to ensure replication initiation during S phase. Because replication initiation is regulated by multiple biological cues, additional changes to MCM may provide better understanding towards this event. Here, we report that histidine methyltransferase SETD3 promotes DNA replication in a manner dependent on enzymatic activity. Nascent-strand sequencing (NS-seq) shows that SETD3 regulates replication initiation, as depletion of SETD3 attenuates early replication origins firing. Biochemical studies reveal that SETD3 binds MCM mainly during S phase, which is required for the CDT1-mediated chromatin loading of MCM. This MCM loading relies on histidine-459 methylation (H459me) on MCM7 which is catalyzed by SETD3. Impairment of H459 methylation attenuates DNA synthesis and chromatin loading of MCM. Furthermore, we show that CDK2 phosphorylates SETD3 at Serine-21 during the G1/S phase, which is required for DNA replication and cell cycle progression. These findings demonstrate a novel mechanism by which SETD3 methylates MCM to regulate replication initiation.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"793-808"},"PeriodicalIF":8.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142507077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The dark activity of Arabidopsis blue-light receptor CRY2.","authors":"Gao-Ping Qu, Zeru Zhang, Chentao Lin","doi":"10.1007/s11427-024-2788-y","DOIUrl":"10.1007/s11427-024-2788-y","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"887-889"},"PeriodicalIF":8.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dawit Adisu Tadese, James Mwangi, Lei Luo, Hao Zhang, Xiaoshan Huang, Brenda B Michira, Shengwen Zhou, Peter Muiruri Kamau, Qiumin Lu, Ren Lai
{"title":"The microbiome's influence on obesity: mechanisms and therapeutic potential.","authors":"Dawit Adisu Tadese, James Mwangi, Lei Luo, Hao Zhang, Xiaoshan Huang, Brenda B Michira, Shengwen Zhou, Peter Muiruri Kamau, Qiumin Lu, Ren Lai","doi":"10.1007/s11427-024-2759-3","DOIUrl":"10.1007/s11427-024-2759-3","url":null,"abstract":"<p><p>In 2023, the World Obesity Atlas Federation concluded that more than 50% of the world's population would be overweight or obese within the next 12 years. At the heart of this epidemic lies the gut microbiota, a complex ecosystem that profoundly influences obesity-related metabolic health. Its multifaced role encompasses energy harvesting, inflammation, satiety signaling, gut barrier function, gut-brain communication, and adipose tissue homeostasis. Recognizing the complexities of the cross-talk between host physiology and gut microbiota is crucial for developing cutting-edge, microbiome-targeted therapies to address the global obesity crisis and its alarming health and economic repercussions. This narrative review analyzed the current state of knowledge, illuminating emerging research areas and their implications for leveraging gut microbial manipulations as therapeutic strategies to prevent and treat obesity and related disorders in humans. By elucidating the complex relationship between gut microflora and obesity, we aim to contribute to the growing body of knowledge underpinning this critical field, potentially paving the way for novel interventions to combat the worldwide obesity epidemic.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"657-672"},"PeriodicalIF":8.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dake Xiao, Haowen Ran, Lishu Chen, Yuanyuan Li, Yan Cai, Songyang Zhang, Qinghui Qi, Huiran Wu, Cheng Zhang, Shuailiang Cao, Lanjuan Mi, Haohao Huang, Ji Qi, Qiuying Han, Haiqing Tu, Huiyan Li, Tao Zhou, Fangye Li, Ailing Li, Jianghong Man
{"title":"FSD1 inhibits glioblastoma diffuse infiltration through restriction of HDAC6-mediated microtubule deacetylation.","authors":"Dake Xiao, Haowen Ran, Lishu Chen, Yuanyuan Li, Yan Cai, Songyang Zhang, Qinghui Qi, Huiran Wu, Cheng Zhang, Shuailiang Cao, Lanjuan Mi, Haohao Huang, Ji Qi, Qiuying Han, Haiqing Tu, Huiyan Li, Tao Zhou, Fangye Li, Ailing Li, Jianghong Man","doi":"10.1007/s11427-024-2616-7","DOIUrl":"10.1007/s11427-024-2616-7","url":null,"abstract":"<p><p>The infiltration of glioblastoma multiforme (GBM) is predominantly characterized by diffuse spread, contributing significantly to therapy resistance and recurrence of GBM. In this study, we reveal that microtubule deacetylation, mediated through the downregulation of fibronectin type III and SPRY domain-containing 1 (FSD1), plays a pivotal role in promoting GBM diffuse infiltration. FSD1 directly interacts with histone deacetylase 6 (HDAC6) at its second catalytic domain, thereby impeding its deacetylase activity on α-tubulin and preventing microtubule deacetylation and depolymerization. This inhibitory interaction is disrupted upon phosphorylation of FSD1 at its Ser317 and Ser324 residues by activated CDK5, leading to FSD1 dissociation from microtubules and facilitating HDAC6-mediated α-tubulin deacetylation. Furthermore, increased expression of FSD1 or interference with FSD1 phosphorylation reduces microtubule deacetylation, suppresses invasion of GBM stem cells, and ultimately mitigates tumor infiltration in orthotopic GBM xenografts. Importantly, GBM tissues exhibit diminished levels of FSD1 expression, correlating with microtubule deacetylation and unfavorable clinical outcomes in GBM patients. These findings elucidate the mechanistic involvement of microtubule deacetylation in driving GBM cell invasion and offer potential avenues for managing GBM infiltration.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"673-688"},"PeriodicalIF":8.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Insufficient MIRO1 contributes to declined oocyte quality during reproductive aging.","authors":"Zhen-Nan Pan, Hao-Lin Zhang, Kun-Huan Zhang, Jia-Qian Ju, Jing-Cai Liu, Shao-Chen Sun","doi":"10.1007/s11427-024-2700-5","DOIUrl":"10.1007/s11427-024-2700-5","url":null,"abstract":"<p><p>Mitochondrial Rho-GTPase 1 (MIRO1) is an outer mitochondrial membrane protein which regulates mitochondrial transport and mitophagy in mitosis. In present study, we reported the crucial roles of MIRO1 in mammalian oocyte meiosis and its potential relationship with aging. We found that MIRO1 expressed in mouse and porcine oocytes, and its expression decreased in aged mice. MIRO1 deficiency caused the failure of meiotic resumption and polar body extrusion in both mouse and porcine oocytes, which could be rescued by exogenous MIRO1 supplementation. Mass spectrometry data indicated that MIRO1 associated with several cytoskeleton and cell cycle-related proteins, and MIRO1 regulated motor protein Dynein for microtubule-organizing centers (MTOCs) dynamics at germinal vesicle (GV) stage, which determined meiotic resumption. Furthermore, we found that MIRO1 regulated Aurora A and kinesin family member 11 (KIF11) for meiotic spindle assembly in oocytes. Besides, MIRO1 associated with several mitochondria-related proteins dynamic-related protein 1 (DRP1), Parkin and lysosomal-associated membrane protein 2 (LAMP2) for mitochondrial dynamics and mitophagy during oocyte meiosis. Taken together, our results suggested that MIRO1 played pivotal roles in meiotic resumption, spindle assembly and mitochondrial function in mouse and porcine oocytes, and its insufficiency might contribute to the oocyte maturation defects during aging.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"764-776"},"PeriodicalIF":8.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Microbial production of chondroitin sulfate and its derivatives.","authors":"Jine Li, Jihui Zhang, Huarong Tan","doi":"10.1007/s11427-024-2805-1","DOIUrl":"10.1007/s11427-024-2805-1","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"871-873"},"PeriodicalIF":8.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Integrating spatial transcriptomics and single-nucleus RNA-seq revealed the specific inhibitory effects of TGF-β on intramuscular fat deposition.","authors":"Xiaoyu Wang, Chuchu Chen, Chenggan Li, Xiaochang Chen, Rong Xu, Meilin Chen, Yongpeng Li, Yihao Liu, Xiaohong Liu, Yaosheng Chen, Delin Mo","doi":"10.1007/s11427-024-2696-5","DOIUrl":"10.1007/s11427-024-2696-5","url":null,"abstract":"<p><p>Intramuscular fat (IMF) is a complex adipose tissue within skeletal muscle, appearing specially tissue heterogeneous, and the factors influencing its formation remain unclear. In conditions such as diabetes, aging, and muscle wasting, IMF was deposited in abnormal locations in skeletal muscle, damaged the normal physiological functions of skeletal muscle. Here, we used Longissimus dorsi muscles from pigs with different IMF contents as samples and adopted a method combining spatial transcriptome (ST) and single-nucleus RNA-seq to identify the spatial heterogeneity of IMF. ST revealed that genes involved in TGF-β signaling pathways were specifically highly enriched in IMF. In lean pigs, IMF autocrine produces more TGF-β2, while in obese pigs, IMF received more endothelial-derived TGF-β1. In vitro experiments have proven that porcine endothelial cells in a simulated high-fat environment released more TGF-β1 than TGF-β2. Moreover, under obesity mice, the addition of TGF-β after muscle injury abolished IMF production and slowed muscle repair, whereas TGF-β inhibition accelerated muscle repair. Our findings demonstrate that the TGF-β pathway specifically regulates these processes, suggesting it as a potential therapeutic target for managing muscle atrophy in obese patients and enhancing muscle repair while reducing IMF deposition.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"746-763"},"PeriodicalIF":8.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"An insect cell-derived extracellular vesicle-based gB vaccine elicits robust adaptive immune responses against Epstein-Barr virus.","authors":"Qian Wu, Kaiyun Chen, Wenhui Xue, Guosong Wang, Yanbo Yang, Shaowei Li, Ningshao Xia, Yixin Chen","doi":"10.1007/s11427-023-2599-1","DOIUrl":"10.1007/s11427-023-2599-1","url":null,"abstract":"<p><p>Epstein-Barr virus (EBV), the first identified human tumor virus, is implicated in various human malignancies, infectious mononucleosis, and more recently, multiple sclerosis. Prophylactic vaccines have the potential to effectively prevent EBV infection. Glycoprotein B (gB) serves as the fusogen and plays a pivotal role in the virus entry process, making it a critical target for EBV vaccine development. Surface membrane proteins of enveloped viruses serve as native conformational antigens, making them susceptible to immune recognition. Utilizing lipid membrane-bound viral antigens is a promising strategy for effective vaccine presentation in this context. In this study, we employed a truncated design for gB proteins, observing that these truncated gB proteins prompted a substantial release of extracellular vesicles (EVs) in insect cells. We verified that EVs exhibited abundant gB proteins, displaying the typical virus particle morphology and extracellular vesicle characteristics. gB EVs demonstrated a more efficient humoral and cellular immune response compared with the gB ectodomain trimer vaccine in mice. Moreover, the antisera induced by the gB EVs vaccine exhibited robust antibody-dependent cytotoxicity. Consequently, gB EVs-based vaccines hold significant potential for preventing EBV infection and offer valuable insights for vaccine design.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"734-745"},"PeriodicalIF":8.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Construction of a lightweight, bispecific human antibody based on the bovine nano knob domain.","authors":"Siling Wang, Yizhen Wang, Xiuting Chen, Wenling Jiang, Zheng Chen, Huixian Shang, Zhiyong Li, Zizheng Zheng, Ningshao Xia","doi":"10.1007/s11427-024-2644-3","DOIUrl":"10.1007/s11427-024-2644-3","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"877-879"},"PeriodicalIF":8.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wenqian Li, Guoxiong Han, Xiaorui Wang, Kuo Shen, Youbang Xie
{"title":"Identification of EPOR and JAK2 double heterozygous variants in twin cases with familial erythrocytosis.","authors":"Wenqian Li, Guoxiong Han, Xiaorui Wang, Kuo Shen, Youbang Xie","doi":"10.1007/s11427-024-2786-5","DOIUrl":"10.1007/s11427-024-2786-5","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"880-883"},"PeriodicalIF":8.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}