Cell Proliferation最新文献

{"title":"Decoding the Molecular Landscape of Prepubertal Oocyte Maturation: GTPBP4 as a Key Driver of In Vitro Developmental Competence.","authors":"Jianpeng Qin, Yaozong Wei, Ao Ning, Wenqi Hu, Pengcheng Wan, Beijia Cao, Bo Pan, Tianyi Lv, Kunlin Du, Xueling Yao, Shuqi Zou, Xiangyi Chen, Shengqin Zang, Jiangfeng Ye, Guozhi Yu, Qiuxia Liang, Liuhong Shen, Lin Zhang, Xiang Chen, Keren Cheng, Li Meng, Guangbin Zhou","doi":"10.1111/cpr.70017","DOIUrl":"https://doi.org/10.1111/cpr.70017","url":null,"abstract":"<p><p>The intricate mechanisms driving oocyte maturation remain only partially understood, especially within the domains of domestic animal reproduction and translational medicine. In the case of prepubertal girls, the clinical challenge is especially pronounced, as ovarian tissue cryopreservation-though promising-remains an experimental technique necessitating rigorous scientific validation to guarantee the developmental potential of preserved materials and facilitate broader clinical adoption. To address these knowledge gaps, while considering the ethical implications, we applied transcriptome and translatome sequencing to comprehensively profile the transcriptional and translational dynamics of oocyte maturation in adult and prepubertal goats. Our analyses uncovered a sequential transition in gene expression regulation, shifting from cytoplasmic processes to chromosome segregation during the maturation process. Comparative profiling between adult and prepubertal goat oocytes revealed critical regulatory factors essential for prepubertal oocyte maturation. These include genes involved in organelle function (GTPBP4 and TOMM7), spindle organisation (CKS2, CCP110, CKAP5 and ESCO1) and chromosome segregation (CENPE, CENPF, CENPN and SGO2). Functional validation through in vitro maturation experiments demonstrated that GTPBP4 significantly enhances the developmental competence of prepubertal goat oocytes. This enhancement occurs through mechanisms that promote cell cycle progression, organelle maturation and mRNA translation. These findings provide a detailed map of the molecular events underpinning goat oocyte maturation and offer new perspectives on the developmental strategies required for oocyte competence in prepubertal females. Translating these insights to humans, this research highlights potential fertility preservation strategies for prepubertal girls, such as ovarian tissue cryopreservation and transplantation, in vitro follicle culture, meiotic maturation and artificial ovary technologies. Moreover, the identified mechanisms have significant implications for improving reproductive efficiency in domestic animal breeding, bridging basic research and applied science.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70017"},"PeriodicalIF":5.9,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522669","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":"Prime Editing: A Revolutionary Technology for Precise Treatment of Genetic Disorders","authors":"Mengyao Li,&nbsp;Yi Lin,&nbsp;Qiang Cheng,&nbsp;Tuo Wei","doi":"10.1111/cpr.13808","DOIUrl":"10.1111/cpr.13808","url":null,"abstract":"<p>Genetic diseases have long posed significant challenges, with limited breakthroughs in treatment. Recent advances in gene editing technologies offer new possibilities in gene therapy for the treatment of inherited disorders. However, traditional gene editing methods have limitations that hinder their potential for clinical use, such as limited editing capabilities and the production of unintended byproducts. To overcome these limitations, prime editing (PE) has been developed as a powerful tool for precise and efficient genome modification. In this review, we provide an overview of the latest advancements in PE and its potential applications in the treatment of inherited disorders. Furthermore, we examine the current delivery vehicles employed for delivering PE systems in vitro and in vivo, and analyze their respective benefits and limitations. Ultimately, we discuss the challenges that need to be addressed to fully unlock the potential of PE for the remission or cure of genetic diseases.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"58 4","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13808","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522671","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}

{"title":"Environmental Drivers of Malignant Clonal Selection in Precancerous Lesion Evolution.","authors":"Yancheng Lai, Shaosen Zhang","doi":"10.1111/cpr.70011","DOIUrl":"https://doi.org/10.1111/cpr.70011","url":null,"abstract":"<p><p>Somatic mutations accumulation and subsequent malignant clonal selection are the processes that lead to cancer. The intricacy includes exposure to carcinogens as well as the ways in which these exposures interact with genetic, polygenic, or epigenetic predispositions. It is worthwhile to investigate how environmental factors influence the initial transformation of healthy cells into malignant ones, or their effects on promoting growth, invasion, immune evasion, inflammation and drug resistance of onset cancerous cells.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70011"},"PeriodicalIF":5.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499178","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":"Stroke-Homing Peptide-DNase1 Alleviates Intestinal Ischemia Reperfusion Injury by Selectively Degrading Neutrophil Extracellular Traps.","authors":"Tingting Liu, Xinrong Lv, Qingshan Xu, Xiuting Qi, Shenghui Qiu, Yaqi Luan, Na Shen, Jing Cheng, Lan Jin, Tian Tian, Wentao Liu, Lai Jin, Zhongzhi Jia","doi":"10.1111/cpr.70010","DOIUrl":"https://doi.org/10.1111/cpr.70010","url":null,"abstract":"<p><p>Neutrophil extracellular traps (NETs) act as a vital first line of defence against tissue damage and pathogens, playing a significant role in improving diseases such as intestinal ischemia reperfusion injury (IRI). However, we observed that after intestinal injury, intestinal bacteria and lipopolysaccharides (LPS) can enter the circulatory system, leading to a significant secondary increase in NETs production and the subsequent activation of a coagulation cascade. This phenomenon contributes to a pathological process known as the 'second strike' of NETs, which exaggerates intestinal damage and microcirculation disturbance. Selectively mitigating the detrimental effects associated with this second strike presents a promising therapeutic strategy. We developed an innovative conjugate of stroke-homing peptide (SHp) and DNase1 (SHp-DNase1) to enhance the stability of DNase in the bloodstream while selectively targeting NETs in thromboembolic events. The effects of SHp-DNase1 on blood flow, ischemia, and vascular leakage were evaluated in a mouse model using laser Doppler flowmetry and an in vivo imaging system. Levels of LPS and NETs were elevated in patients with IRI. Similarly, the expression of NETs and LPS was upregulated in mice with intestinal IRI. In vivo imaging revealed disturbances in intestinal microcirculation, accompanied by intestinal leakage, which were effectively reversed by the administration of SHp-DNase1. Almost all of the SHp-DNase1 localised to the gastrointestinal tract, demonstrating the effective targeting of DNase1 to the site of intestinal injury via SHp guidance. Furthermore, the combination of SHp-DNase1 and CRO significantly reduced the expression of ischemia-inducible factors, leading to a marked decrease in mortality in the mouse model. These findings suggest that intestinal LPS leakage correlated with NETs exacerbation plays a critical role in IRI. The combination of SHp-DNase1 and CRO is an effective treatment strategy by simultaneously controlling inflammation and addressing microcirculatory disorders induced by NETs in the therapy of IRI.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70010"},"PeriodicalIF":5.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499218","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":"Advances in the Study of Pluripotent Stem Cells in Livestock.","authors":"Xinyi Zhou, Chen Gao, Wenxuan Zhao, Xinhua Wei, Dawei Yu, Huiying Zou, Weihua Du","doi":"10.1111/cpr.70008","DOIUrl":"https://doi.org/10.1111/cpr.70008","url":null,"abstract":"<p><p>Livestock pluripotent stem cells, derived either from early embryos or induced through somatic cell reprogramming technology, possess the unique ability to self-renew, maintain an undifferentiated state and differentiate into various cell types. Consequently, the generation of PSCs from agricultural animal species holds great potential for applications in livestock breed improvement, rapid propagation, disease modelling and xenotransplantation. However, compared to the great achievements made in mouse and human pluripotent stem cells research, the generation of livestock pluripotent stem cells still remains challenging. This article offers an overview of the classification, regulatory mechanisms of pluripotency, and developmental history of livestock pluripotent stem cells, while also anticipating their future application prospects. These insights provide valuable references for the reproduction and breeding of large livestock.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70008"},"PeriodicalIF":5.9,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490973","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":"tRF-3a-Pro: A Transfer RNA-Derived Small RNA as a Novel Biomarker for Diagnosis of Hepatitis B Virus-Related Hepatocellular Carcinoma.","authors":"Jingyi Si, Yanting Zou, Yifan Gao, Jia Chen, Wei Jiang, Xizhong Shen, Changfeng Zhu, Qunyan Yao","doi":"10.1111/cpr.70006","DOIUrl":"https://doi.org/10.1111/cpr.70006","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is one of the most challenging malignancies of the digestive system. Screening for novel biomarkers and therapeutic targets is a promising strategy to enhance HCC prognosis. Recently, liquid biopsy with circulating nucleic acids as the detection targets has attracted much attention in the field of early screening of tumours. However, the diagnostic value and biological functions of transfer RNA-derived small RNAs (tsRNAs) in serum, particularly in HCC, remains unknown. In this study, we characterised the expression profile of tsRNAs in hepatitis B virus (HBV)-related HCC, and confirmed the diagnostic potential of serum tRF-3a-Pro. On this basis, we established a diagnostic model that integrates tRF-3a-Pro with the classic HCC biomarker alpha-fetoprotein (AFP) through logistic regression analysis. Besides, both in vivo and in vitro experiments demonstrated that tRF-3a-Pro, a highly expressed tsRNA, promotes HCC cell proliferation. These findings suggested that tRF-3a-Pro could serve as a novel biomarker for HBV-related HCC.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70006"},"PeriodicalIF":5.9,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490974","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":"Mitochondrial Mutation Leads to Cardiomyocyte Hypertrophy by Disruption of Mitochondria-Associated ER Membrane.","authors":"Miao Yu, Min Song, Manna Zhang, Shuangshuang Chen, Baoqiang Ni, Xuechun Li, Wei Lei, Zhenya Shen, Yong Fan, Jianyi Zhang, Shijun Hu","doi":"10.1111/cpr.70002","DOIUrl":"https://doi.org/10.1111/cpr.70002","url":null,"abstract":"<p><p>m.3243A>G is the most common pathogenic mtDNA mutation. High energy-demanding organs, such as heart, are usually involved in mitochondria diseases. However, whether and how m.3243A>G affects cardiomyocytes remain unknown. We have established patient-specific iPSCs carrying m.3243A>G and induced cardiac differentiation. Cardiomyocytes with high m.3243A>G burden exhibited hypertrophic phenotype. This point mutation is localised in MT-TL1 encoding tRNA^{Leu (UUR)}. m.3243A>G altered tRNA^{Leu (UUR)} conformation and decreased its stability. mtDNA is essential for mitochondrial function. Mitochondria dysfunction occurred and tended to become round. Its interaction with ER, mitochondria-associated ER membrane (MAM), was disrupted with decreased contact number and length. MAM is a central hub for calcium trafficking. Disrupted MAM disturbed calcium homeostasis, which may be the direct and leading cause of cardiomyocyte hypertrophy, as MAM enforcement reversed this pathological state. Considering the threshold effect of mitochondrial disease, mito-TALENs were introduced to eliminate mutant mitochondria and release mutation load. Mutation reduction partially reversed the cellular behaviour and made it approach to that of control one. These findings reveal the pathogenesis underlying m.3243A>G from perspective of organelle interaction, rather than organelle. Beyond mitochondria quality control, its proper interaction with other organelles, such as ER, matters for mitochondria disease. This study may provide inspiration for mitochondria disease intervention.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70002"},"PeriodicalIF":5.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467200","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":"SIRT1 Alleviates Oxidative Stress-Induced Mitochondrial Dysfunction and Mitochondria-Associated Membrane Dysregulation in Stress Urinary Incontinence.","authors":"Liying Chen, Jianming Tang, Xiaohu Zuo, Bingshu Li, Cheng Liu, Shasha Hong, Jie Min, Ming Hu, Suting Li, Min Zhou, Mao Chen, Yong He, Ya Xiao, Xiaoyu Huang, Li Hong","doi":"10.1111/cpr.70009","DOIUrl":"https://doi.org/10.1111/cpr.70009","url":null,"abstract":"<p><p>The pathogenesis of stress urinary incontinence (SUI), a condition common in women, remains to be fully elucidated. This study revealed that the incidence of SUI is associated with mitochondrial homeostasis dysregulation following oxidative stress in the fibrous connective tissue of the pelvic floor. SIRT1 is an essential factor for maintaining mitochondrial homeostasis; however, its potential role and mechanism of action in SUI pathogenesis remain unclear. Both in vitro and in vivo, we observed that oxidative stress reduced SIRT1 expression to inhibit the PGC-1α/NRF1/TFAM and PINK1/Parkin signalling pathways, eliciting impairment of mitochondrial biogenesis and mitophagy in L929 cells and SUI mice. Decreased SIRT1 levels induced endoplasmic reticulum (ER) stress and altered the structure of mitochondria-associated membranes (MAMs), disrupting ER-mitochondrial calcium homeostasis and exacerbting ROS accumulation. SIRT1 activation can restore mitochondrial function and the structure of MAMs and alleviate ER stress in fibroblasts, promoting anterior vaginal wall repair and improving urodynamic parameters in the SUI model. Our findings provide novel insights into the role and associated mechanism of SIRT1 in ameliorating oxidative stress-induced mitochondrial dysfunction in fibroblasts of the anterior vaginal wall and propose SIRT1 as a potential therapeutic target for SUI.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70009"},"PeriodicalIF":5.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467202","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":"Human Midbrain Organoids Enriched With Dopaminergic Neurons for Long-Term Functional Evaluation.","authors":"Xinyue Wang, Gaoying Sun, Mingming Tang, Da Li, Jianhuan Qi, Chuanyue Wang, Yukai Wang, Baoyang Hu","doi":"10.1111/cpr.70005","DOIUrl":"https://doi.org/10.1111/cpr.70005","url":null,"abstract":"<p><p>Human midbrain organoids with functional dopaminergic (DA) neurons are invaluable for the therapeutic development of Parkinson's disease (PD). However, current methods face significant limitations, including challenges in generating pint-sized organoids enriched with DA neurons and the lack of robust functional assays for efficiently evaluating neural networks over extended periods. Here we present an innovative approach that combines developmental patterning with mechanical cutting to produce small midbrain organoids, with diameters less than 300 μm, suitable for long-term evaluation, along with a comprehensive functional assay system consisting of calcium transient assay, neurite extension assay, and multielectrode array (MEA) assay. Radial cutting of organoids into four to eight portions according to their sizes at the appropriate developmental stage significantly increases the yield of viable organoids while reducing necrotic cell regions. Using the functional assay system, we demonstrate that DA neurons within the organoids extend long projections, respond to dopamine stimulation, and form neural networks characterised by giant depolarising potential-like events. Our approach supports the generation of midbrain organoids and PD models that can be used for long-term functional testing.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70005"},"PeriodicalIF":5.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456664","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":"Organoid Models to Study Human Infectious Diseases.","authors":"Sijing Zhu, Dan Chen, Xinzhi Yang, Liuliu Yang, Yuling Han","doi":"10.1111/cpr.70004","DOIUrl":"https://doi.org/10.1111/cpr.70004","url":null,"abstract":"<p><p>Infectious diseases have become significant events that threaten global public health and economic development. Since the 20th century, multiple outbreaks of infectious diseases have gradually deepened humanity's understanding of viral infections, prevention and treatment. Organoids possess a high degree of similarity to human physiological states and have strong self-organising capabilities. Research on infectious diseases based on organoids offers significant advantages in terms of availability, editability and diversity. In this perspective, we briefly introduce the development of organoids, focusing on historically significant infectious diseases that have caused fatal harm to human health, such as HIV, ZIKV, SARS-CoV-2 and MPXV. We further summarise relevant research on the pathogenic mechanisms of these viruses based on organoid models, host reactivity, and therapeutic strategies. Finally, we list the latest research techniques combined with organoid models, discuss the challenges faced in the development of organoids and look forward to the future prospects of organoids in vaccine and drug development.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70004"},"PeriodicalIF":5.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456675","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}