Cell Proliferation最新文献

{"title":"RNF187 Facilitates Proliferation and Migration of Human Spermatogonial Stem Cells Through WDR77 Polyubiquitination.","authors":"Haoyue Hu, Xiaoxue Xi, Bing Jiang, Kehan Wang, Tiantian Wu, Xia Chen, Yueshuai Guo, Tao Zhou, Xiaoyan Huang, Jun Yu, Tingting Gao, Yibo Wu, Bo Zheng","doi":"10.1111/cpr.70042","DOIUrl":"https://doi.org/10.1111/cpr.70042","url":null,"abstract":"<p><p>The E3 ubiquitin ligase RNF187, also known as RING domain AP1 coactivator-1, is a member of the RING finger family. RNF187 is indispensable for the proliferation and migration of GC-1 cells derived from mouse spermatogonia and GC-2 cells derived from spermatocytes. However, it remains unclear whether RNF187 plays a crucial role in the self-renewal and migration of human spermatogonial stem cells (SSCs). In this study, we observed a positive correlation between RNF187 expression and the proliferation and migration of human SSCs. Through co-immunoprecipitation and mass spectrometry analyses, we identified WD repeat-containing protein 77 (WDR77) as an interacting partner of RNF187. Specifically, RNF187 recognises the K118 site of WDR77 through lysine 48-linked polyubiquitination, subsequently mediating its degradation via the ubiquitin-proteasome system (UPS). Further studies have revealed that decreased expression of WDR77 diminishes the symmetric dimethylation at H4R3 (H4R3me2s) catalysed by its interacting protein, the arginine methyltransferase PRMT5. This, in turn, relieves the transcriptional repression of early growth response protein 1 (EGR1), a positive regulator for human SSC maintenance. In conclusion, this study has unveiled a pivotal role for RNF187 in the proliferation and migration of human SSCs. This may provide a promising strategy for addressing non-obstructive azoospermia (NOA) caused by SSC dysfunction.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70042"},"PeriodicalIF":5.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802627","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":"Production and Functional Verification of 8-Gene (GGTA1, CMAH, β4GalNT2, hCD46, hCD55, hCD59, hTBM, hCD39)-Edited Donor Pigs for Xenotransplantation.","authors":"Jiaoxiang Wang, Kaixiang Xu, Tao Liu, Heng Zhao, Muhammad Ameen Jamal, Gen Chen, Xiaoying Huo, Chang Yang, Deling Jiao, Taiyun Wei, Hanfei Huang, Hongfang Zhao, Jianxiong Guo, Fengchong Wang, Xiong Zhang, Kai Liu, Siming Qu, Gang Wang, Hui Guo, Gang Chen, Hong-Ye Zhao, Zhong Zeng, Kefeng Dou, Hong-Jiang Wei","doi":"10.1111/cpr.70028","DOIUrl":"https://doi.org/10.1111/cpr.70028","url":null,"abstract":"<p><p>Gene-edited (GE) pig-to-human xenotransplantation continues to make breakthroughs, but which kind of gene combination is suitable for organ-specific transplantation remains unclear. In this study, we utilised CRISPR/Cas9 gene editing technology, PiggyBac transposon system, and serial somatic cell cloning technology to develop GTKO/CMAHKO/β4GalNT2KO/hCD46/hCD55/hCD59/hCD39/hTBM 8 gene-edited cloned (GEC) donor pigs and performed pig-to-non-human primate (NHP) transplantation to evaluate the effectiveness of these GEC pigs. The 8-GEC pigs were obtained by recloning with a 33-day-old 8-GEC fetus with O blood type, which was generated after cell transfection, screening of cell colonies, and somatic cell cloning. Molecular identification at DNA, mRNA, and protein levels confirmed successful 8-gene editing. Three copies of transgenes were identified by droplet digital polymerase chain reaction and whole genome sequencing, which were inserted into the introns of pig RFTN1 and MYO10 genes, as well as the intergenic region between PRLR and LOC110257300 genes of these 8-GEC pigs. The 8-GEC pigs also exhibited the ability of germline transmission when mated with our previously generated 4-GEC male pigs. Moreover, antigen-antibody binding assay and complement-dependent cytotoxicity assay demonstrated that 8-gene editing effectively reduced the immune incompatibility and kidney xenograft from 8-GEC pigs survived for 15 and 17 days in two NHPs, respectively. Postoperatively, the recipient serum antibodies IgA, IgG and IgM, complements C3 and C4, coagulation indicators PT, APTT, TT and FIB, as well as most electrolytes and liver function indicators remained relatively stable. Serum creatinine was normal within 10 days post operation. However, the kidney xenograft developed active antibody-mediated rejection at necropsy, characterised by the deposition of antibodies IgG and IgM, as well as complements C4d, C3c and C5b-C9, infiltration of CD68⁺ macrophages, and micro-thrombotic embolism of glomerular capillaries, etc. In conclusion, we successfully developed fertile 8-GEC pigs, which effectively alleviated immune rejection and exerted life-supporting kidney function in the recipients.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70028"},"PeriodicalIF":5.9,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794612","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":"Featured Cover","authors":"Mei Xu,&nbsp;Dian Gan,&nbsp;Xi-Yu Zhang,&nbsp;Xiao-Tao He,&nbsp;Rui Xin Wu,&nbsp;Yuan Yin,&nbsp;Rui Jin,&nbsp;Lin Li,&nbsp;Yu-Jie Tan,&nbsp;Fa-Ming Chen,&nbsp;Xuan Li,&nbsp;Bei-Min Tian","doi":"10.1111/cpr.70038","DOIUrl":"https://doi.org/10.1111/cpr.70038","url":null,"abstract":"<p>The cover image is based on the article <i>SLC30A4-AS1 Mediates the Senescence of Periodontal Ligament Stem Cells in Inflammatory Environments via the Alternative Splicing of TP53BP1</i> by Mei Xu et al., https://doi.org/10.1111/cpr.13778.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"58 4","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.70038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770325","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":"Correction to \"Shiga-Like Toxin I Exerts Specific and Potent Anti-Tumour Efficacy Against Gastric Cancer Cell Proliferation When Driven by Tumour-Preferential Frizzled-7 Promoter\".","authors":"","doi":"10.1111/cpr.70030","DOIUrl":"https://doi.org/10.1111/cpr.70030","url":null,"abstract":"","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70030"},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763186","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":"Scalable Matrigel-Free Suspension Culture for Generating High-Quality Human Liver Ductal Organoids.","authors":"Senyi Gong, Kangxin He, Yu Liu, Xingyu Luo, Kamran Ashraf, Jinzhao He, Weifeng Li, Lihua Yang, Touseef Ur Rehman, Mingwei Shen, Qinbiao Yan, Ali Mohsin, Shusen Zheng, Zhe Yang, Meijin Guo","doi":"10.1111/cpr.70033","DOIUrl":"https://doi.org/10.1111/cpr.70033","url":null,"abstract":"<p><p>Liver transplantation is currently the sole definitive treatment option for end-stage liver failure. However, a significant shortage of donors prevails due to high clinical demands. Recently, human liver organoids have shown significant potential in regenerative medicine for liver diseases. Nevertheless, current static cultures of organoids grown in well-plates heavily rely on extracellular matrix hydrogels (Matrigel), thereby limiting both the scalability and quantity of organoid culture. In this study, we present a groundbreaking culture mode that eliminates all reliance on extracellular matrix hydrogels, enabling the successful preparation of functional human liver ductal organoids (LDOs) based on the cell suspension culture mode in a mechanically stirred bioreactor. Initially, the developed suspension culture in a 6-well plate without matrigel was proven to support robust growth of liver ductal organoids with an average size 2.6 times larger than those obtained in static culture, and with a high organoid survival rate exceeding 90%. Also, the transcriptome profile reveals that suspension culture activates the phosphatidylinositol 3-kinase (PI3K) signalling pathway through mechanical signal transduction, thereby promoting hepatobiliary characteristics. Then, a controllable and scalable bioprocess for liver ductal organoid culture was developed and successfully scaled up to a 50 mL flask bioreactor with a working volume of 15 mL. Finally, animal experiments indicated that the transplantation of liver ductal organoids harvested from suspension culture can effectively alleviate liver injury and inflammation, demonstrating the feasibility of large-scale production of liver ductal organoids cultivated in suspension culture with an improved extracellular matrix environment.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70033"},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751341","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":"Targeting SHP-1-Mediated Inhibition of STAT3 and ERK Signalling Pathways Rescues the Hyporesponsiveness of MHC-I-Deficient NK-92MI.","authors":"Kuo Yu, Xiaolong Liu, Guangyuan Wu, Zhongyao An, Xin Wang, Yang Liu, Hailong Wang, Mingli Huang, Linlin Zhao, Ce Shi, Xin Sun, Lu Xu, Sen Qi, Xin Zhang, Yueqiu Teng, Song Guo Zheng, Zhiren Zhang, Zhenkun Wang","doi":"10.1111/cpr.70035","DOIUrl":"https://doi.org/10.1111/cpr.70035","url":null,"abstract":"<p><p>Natural Killer (NK) cells have shown promising prospects in 'off-the-shelf' cell therapy, particularly the NK-92 cell line, which can serve as a foundation for the next generation of universal chimeric antigen receptor (CAR)-engineered NK products. A key strategy for generating universal cellular products is the elimination of the beta-2-microglobulin (B2M) gene, which encodes a component of MHC class I molecules (MHC-I) that plays a role in the presentation of foreign antigens and in the 'licensing' or 'education' of NK cells. To functionally study the impacts of MHC-I deficiency on NK-92, we generated a B2M knockout (KO) NK-92MI (B-92) cell line and compared the multidimensional properties of B2M KO and wild-type NK-92MI cells in terms of biological phenotypes, effector functions, and transcriptomic signatures. We observed a decrease in activating receptors, cytokine production, and cytotoxicity in B-92 cells. Further analysis of signalling events revealed that the upregulated expression and phosphorylation of SHP-1 in B-92 cells inhibited the phosphorylation levels of STAT3 and ERK, thereby affecting their killing function. By knocking out SHP-1 (PTPN6), we partially restored the cytotoxic function of B-92 cells. Notably, we also found that CAR modification can overcome the hyporesponsiveness of B-92 cells. These findings will facilitate further exploration in the development of NK cell-based products.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70035"},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751345","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":"Accelerating Bone Healing With METTL3 Overexpressed Adipose-Derived Stem Cells in Osteoporotic Rats.","authors":"Hui Tang, Zhenzhen Chen, Lu Zeng, Yuping Xie, Daowen Luo, Shuanglin Peng, Fangzhi Lou, Tianli Wu, Jingang Xiao","doi":"10.1111/cpr.70029","DOIUrl":"https://doi.org/10.1111/cpr.70029","url":null,"abstract":"<p><p>The treatment of postmenopausal osteoporosis (OP) presents a multifaceted challenge. Nonetheless, emerging research indicates a significant association between the N6-methyladenosine (m6A) methylase METTL3 and osteogenesis in OP. To investigate Mettl3's impact on osteogenic potential and the underlying molecular mechanisms, an OP rat model was established via ovariectomy (OVX). Osteoporotic adipose-derived stem cells (OP-ASCs) were then isolated. Results indicated a significant downregulation of Mettl3 expression in OP-ASCs. Subsequently, OP-ASCs were transfected with overexpressed Mettl3 lentivirus and treated for Dickkopf-related protein-1 (DKK1). Overexpression of the Mettl3 gene led to increased levels of osteogenic factors. DKK1 attenuated osteoblastic differentiation capacity in the Mettl3 overexpression group by inhibiting the Wnt signalling pathway. Consistent results were observed in vivo experiments. In conclusion, overexpression of Mettl3 promotes osteogenesis in OP-ASCs by activating the Wnt/β-catenin pathway.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70029"},"PeriodicalIF":5.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691324","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":"Exercise Delays Brain Ageing Through Muscle-Brain Crosstalk.","authors":"Shirin Pourteymour, Rakesh Kumar Majhi, Frode A Norheim, Christian A Drevon","doi":"10.1111/cpr.70026","DOIUrl":"https://doi.org/10.1111/cpr.70026","url":null,"abstract":"<p><p>Ageing is often accompanied by cognitive decline and an increased risk of dementia. Exercise is a powerful tool for slowing brain ageing and enhancing cognitive function, as well as alleviating depression, improving sleep, and promoting overall well-being. The connection between exercise and healthy brain ageing is particularly intriguing, with exercise-induced pathways playing key roles. This review explores the link between exercise and brain health, focusing on how skeletal muscle influences the brain through muscle-brain crosstalk. We examine the interaction between the brain with well-known myokines, including brain-derived neurotrophic factor, macrophage colony-stimulating factor, vascular endothelial growth factor and cathepsin B. Neuroinflammation accumulates in the ageing brain and leads to cognitive decline, impaired motor skills and increased susceptibility to neurodegenerative diseases. Finally, we examine the evidence on the effects of exercise on neuronal myelination in the central nervous system, a crucial factor in maintaining brain health throughout the lifespan.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70026"},"PeriodicalIF":5.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691326","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":"Utilising Human Myometrial and Uterine Fibroid Stem Cell-Derived Three Dimentional Organoids as a Robust Model System for Understanding the Pathophysiology of Uterine Fibroids.","authors":"Mervat M Omran, Somayeh Vafaei, Samar Alkhrait, Farzana Liakath Ali, Maria Victoria Bariani, Tao Bai, Winston E Thompson, Qiwei Yang, Mohamed Ali, Ayman Al-Hendy","doi":"10.1111/cpr.70025","DOIUrl":"https://doi.org/10.1111/cpr.70025","url":null,"abstract":"<p><p>Uterine fibroids (UFs) are the most common benign gynecologic tumours affecting women of reproductive age. This study aims to deepen the understanding of UFs complex aetiology through harnessing the power of 3D organoid models derived from human myometrial stem cells to emulate the in vivo behaviour of these tumours. Isolated SCs were cultured over 7 days under a defined culture system. Immunohistochemistry, Immunofluorescence, organoid stiffness, RNA Sequencing was conducted, and differential gene expression was assessed using RT-PCR. The derived organoids exhibited diverse populations of cells, including stem cells, smooth muscle, and fibroblasts. Excessive ECM deposition was shown via Collagen and Fibronectin expression. We confirmed that our organoids expressed oestrogen receptor in a pattern similar to that in their corresponding tissue, as well as responded to steroid hormone. Interestingly, we revealed significant racial disparities in ECM accumulation within organoids derived from different racial groups. This augmented ECM deposition is theorised to enhance tissue stiffness, as assessed using Young's modulus. Additionally, our research demonstrated significant decreases in fibrotic markers upon treatment with Vitamin D3 and Doxercalciferol. Furthermore, the pro-fibroid effects of environmental phthalates further elucidate the potential factors contributing to UF pathology. The 3D organoid model can serve as a robust platform to study the underlying molecular mechanisms of UFs, besides offering invaluable insights for potential therapeutic interventions.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70025"},"PeriodicalIF":5.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662495","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":"GPD1L-Mediated Glycerophospholipid Metabolism Dysfunction in Women With Diminished Ovarian Reserve: Insights From Pseudotargeted Metabolomic Analysis of Follicular Fluid.","authors":"Jiaqi Wu, Xuehan Zhao, Ying Fang, Cong Wang, Yichang Tian, Wan Tu, Qiqian Wu, Long Yan, Xiaokui Yang","doi":"10.1111/cpr.70024","DOIUrl":"https://doi.org/10.1111/cpr.70024","url":null,"abstract":"<p><p>Diminished ovarian reserve (DOR) is a pathological condition characterised by reduced ovarian function, which refers to the decreased quality and quantity of oocytes, potentially causing female infertility and various health issues. Follicular fluid (FF) serves as the microenvironment for follicular development and oocyte maturation, gaining an in-depth understanding of the metabolic state of FF will help us uncover the key biological processes involved in ovarian aging, while the specific underlying pathogenic mechanisms are not fully understood. In this study, we utilised pseudotargeted metabolomic analysis of FF to reveal the glycerophospholipid metabolism dysfunction mediated by GPD1L in DOR patients. We also found that GPD1L was downregulated in granulosa cells (GCs) of DOR patients, resulting in increased cell apoptosis and mitochondrial dysfunction. Moreover, our results demonstrated that the downregulated expression of GPD1L could induce follicular atresia and impair oocyte quality in mouse ovaries. Altogether, our research suggested that GPD1L in GCs and the key metabolites in the glycerophospholipid metabolism pathway could potentially act as novel biomarkers of DOR diagnosis, paving the way for a new theoretical basis for understanding the pathogenesis of DOR.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70024"},"PeriodicalIF":5.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662492","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}