{"title":"Tetrahedral Framework Nucleic Acid Relieves Sepsis-Induced Intestinal Injury by Regulating M2 Macrophages","authors":"Tingting Tan, Jiajie Li, Wensi Fan, Kangni Shang, Chujun Yang, Xiaohao Liu, Shihui Zhu, Tong Liu, Junjie Wang, Yingchuan Li, Yunfeng Lin","doi":"10.1111/cpr.13803","DOIUrl":"10.1111/cpr.13803","url":null,"abstract":"<p>This study aimed to clarify the role and mechanism of tetrahedral framework nucleic acids (tFNAs) in regulating M2 macrophages to reduce intestinal injury. An intestinal injury model was established by intraperitoneal injection of lipopolysaccharides (LPS) in mice to explore the alleviating effects of tFNAs on intestinal injury. Inflammatory factors were detected by quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). The intestinal barrier and permeability were assessed using western blotting and immunohistochemistry. Macrophages in the gut were localised and quantified using immunofluorescence. Western blotting was used to investigate the role and mechanism of tFNAs in regulating macrophages and alleviating inflammation in the injured intestines. These results show that tFNAs attenuated sepsis-induced intestinal injury. tFNAs can also promote the intestinal barrier reconstruction and reduce intestinal permeability. In vivo, tFNAs accelerated the aggregation of M2 macrophages at an early stage of injury and reduced the number of M1 macrophages in the intestine. In addition, tFNAs enhanced the clearance ability of intestinal macrophages. They activated the signalling and transcription activating factor 1(STAT1) and cytokine signalling inhibitory factor 1/3 (SOCS1/3) pathways by increasing the expression of the phagocytic receptor Mertk. These findings indicated that tFNAs can alleviate sepsis-induced intestinal injury by regulating M2 macrophages, providing a new option for treating intestinal injury.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"58 5","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13803","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022298","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}
Lei Ge, Yali Yang, Yuqing Gao, Tianxia Xiao, Wakam Chang, Hefei Wang, Zhonglin Xiao, Jie Chen, Mengxia Li, Ming Yu, Ping Jin, Jian V. Zhang
{"title":"Ovarian Endometrioma Disrupts Oocyte-Cumulus Communication and Mitochondrial Function, With Melatonin Mitigating the Effects","authors":"Lei Ge, Yali Yang, Yuqing Gao, Tianxia Xiao, Wakam Chang, Hefei Wang, Zhonglin Xiao, Jie Chen, Mengxia Li, Ming Yu, Ping Jin, Jian V. Zhang","doi":"10.1111/cpr.13800","DOIUrl":"10.1111/cpr.13800","url":null,"abstract":"<p>Ovarian endometrioma (OEM), a particularly severe form of endometriosis, is an oestrogen-dependent condition often associated with pain and infertility. The mechanisms by which OEM impairs fertility, particularly through its direct impact on oocyte-cumulus cell (CC) communication and related pathways, remain poorly understood. This study investigates the impact of OEM on oocyte-CC communication and explores melatonin's therapeutic potential. We used a mouse model of OEM and employed ovarian transcriptome and gene set enrichment analyses to identify disrupted gene pathways, alongside phalloidin staining for cytoskeletal analysis, gap junction coupling analysis for intercellular communication, and mitochondrial function assessments for cellular metabolism. Our results showed that OEM significantly impairs steroidogenesis and cumulus cell function, leading to increased apoptosis, disrupted transzonal projections (TZPs), and impaired antioxidant transfer to oocytes. This culminates in oxidative stress, mitochondrial dysfunction, and compromised ATP production. OEM oocytes also exhibited severe abnormalities, including DNA damage, maturation defects, spindle assembly disruptions, and increased aneuploidy. This study identifies disrupted TZPs as a key pathological feature in OEM and highlights melatonin's potential to restore intercellular communication, mitigate oxidative damage, and improve reproductive outcomes.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"58 4","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13800","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000781","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}
Yu Fu, Xin Hao, Peng Shang, Jingru Nie, Yangzom Chamba, Bo Zhang, Hao Zhang
{"title":"MUSTN1 Interaction With SMPX Regulates Muscle Development and Regeneration.","authors":"Yu Fu, Xin Hao, Peng Shang, Jingru Nie, Yangzom Chamba, Bo Zhang, Hao Zhang","doi":"10.1111/cpr.13809","DOIUrl":"https://doi.org/10.1111/cpr.13809","url":null,"abstract":"<p><p>Pigs are important agricultural animals whose growth rate and meat production performance are related to muscle development. Musculoskeletal embryonic nuclear protein 1 (MUSTN1) participates in various biological processes, including myogenesis and growth in animals, but the physiological functions and mechanisms of porcine MUSTN1 on muscle development are unclear; thus, we aimed to elucidate them. We found that MUSTN1 was highly expressed in the muscles of fast-growing pigs. Functionally, MUSTN1 promoted myoblast proliferation and differentiation. MUSTN1 knockout mice exhibited reduced muscle mass and fibre cross-sectional area, decreased exercise endurance, and delayed muscle regeneration. Small muscle protein X-linked (SMPX) was identified as an interacting protein of MUSTN1, and its promotion of myogenic differentiation depended on MUSTN1. Furthermore, MUSTN1 stabilised SMPX and maintained myofiber morphology. This study suggests that MUSTN1 is a critical regulator in the control of muscle development and regeneration and is a potential target for animal genetic improvement and the treatment of human muscle disease.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13809"},"PeriodicalIF":5.9,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000776","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":"Genome-Wide Screening in Haploid Stem Cells Reveals Synthetic Lethality Targeting MLH1 and TP53 Deficient Tumours.","authors":"Rivki Cashman, Guy Haim-Abadi, Elyad Lezmi, Hagit Philip, Jonathan Nissenbaum, Ruth Viner-Breuer, Chen Kozulin, Tamar Golan-Lev, Aseel Gadban, Shiri Spinner-Potesky, Ofra Yanuka, Oded Kopper, Nissim Benvenisty","doi":"10.1111/cpr.13788","DOIUrl":"https://doi.org/10.1111/cpr.13788","url":null,"abstract":"<p><p>Synthetic lethality is defined as a type of genetic interaction where the combination of two genetic events results in cell death, whereas each of them separately does not. Synthetic lethality can be a useful tool in personalised oncology. MLH1 is a cancer-related gene that has a central role in DNA mismatch-repair and TP53 is the most frequently mutated gene in cancer. To identify genetic events that can lead to tumour death once either MLH1 or TP53 is mutated, a genome-wide genetic screening was performed. Thus, mutations in all protein-coding genes were introduced into haploid human embryonic stem cells (hESCs) with and without loss-of-function mutations in the MLH1 or TP53 genes. These experiments uncovered a list of putative hits with EXO1, NR5A2, and PLK2 genes for MLH1, and MYH10 gene for TP53 emerging as the most promising candidates. Synthetic lethal interactions of these genes were validated genetically or chemically using small molecules that inhibit these genes. The specific effects of SR1848, which inhibits NR5A2, ON1231320 or BI2536, which inhibits PLK2, and blebbistatin, which inhibits MYH10, were further validated in cancer cell lines. Finally, animal studies with CCL xenografts showed the selective effect of the small molecule BI2536 on MLH1-null tumours and of blebbistatin on TP53-mutated tumours. Thus, demonstrating their potential for personalised medicine, and the robustness of genetic screening in haploid hESCs in the context of cancer therapeutics.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13788"},"PeriodicalIF":5.9,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000774","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}
Jie Hao, Zhenyi Wang, Jilong Ren, Shenghao Cao, Zhongchen Xie, Jinghuan Yang, Jiachen Li, Weizhe Ding, Jie Li, Zhiqiang Han, Ye Yuan, Tang Hai, Sheng Ding, Michael Q. Zhang, Minglei Shi
{"title":"Single-cell multi-omics deciphers hepatocyte dedifferentiation and illuminates maintenance strategies","authors":"Jie Hao, Zhenyi Wang, Jilong Ren, Shenghao Cao, Zhongchen Xie, Jinghuan Yang, Jiachen Li, Weizhe Ding, Jie Li, Zhiqiang Han, Ye Yuan, Tang Hai, Sheng Ding, Michael Q. Zhang, Minglei Shi","doi":"10.1111/cpr.13772","DOIUrl":"10.1111/cpr.13772","url":null,"abstract":"<p>Due to the similarity to human hepatocytes, porcine hepatocytes play an important role in hepatic research and drug evaluation. However, once hepatocytes were cultured in vitro, it was often prone to dedifferentiate, resulting in the loss of their characteristic features and normal functions, which impede their application in liver transplantation and hepatotoxic drugs evaluation. Up to now, this process has yet to be thoroughly investigated from the single-cell resolution and multi-omics perspective. In this study, we utilized 10× multiome technology to dissect the heterogeneity of porcine hepatocytes at different time points (Days 0, 1, 3, 5 and 7) during dedifferentiation. We comprehensively investigated cell heterogeneity, cellular dynamics, signalling pathways, potential gene targets, enhancer-driven gene regulatory networks, cell–cell communications of these cells and the conservation of mechanisms across species. We found that a series of critical signalling pathways driven by ERK, PI3K, Src and TGF-β were activated during this process, especially in the early stage of dedifferentiation. Based on these discoveries, we constructed a chemical combination targeting these pathways, which effectively inhibited the dedifferentiation of porcine hepatocytes in vitro. To validate the effectiveness of this combination, we transplanted such treated hepatocytes into FRGN mice, and the results demonstrated that these cells could effectively repopulate the liver and improve the survival of mice.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"58 3","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13772","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982922","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}
Gülseren Özduman, Aadil Javed, Azime Akçaöz Alasar, Bünyamin Akgül, Kemal Sami Korkmaz
{"title":"HN1 Functions in Protein Synthesis Regulation via mTOR-RPS6 Axis and Maintains Nucleolar Integrity.","authors":"Gülseren Özduman, Aadil Javed, Azime Akçaöz Alasar, Bünyamin Akgül, Kemal Sami Korkmaz","doi":"10.1111/cpr.13805","DOIUrl":"https://doi.org/10.1111/cpr.13805","url":null,"abstract":"<p><p>Haematological and Neurological Expressed 1 (HN1) is an oncogene for various cancers and previously has been linked with centrosome clustering and cell cycle pathways. Moreover, HN1 has recently been reported to activate mTOR signalling, which is the regulator of ribosome biogenesis and maintenance. We explored the role of HN1 in mTOR signalling through various gain- and loss-of-function experiments using biochemical approaches in different cell lines. We demonstrated for the first time that HN1 is required for nucleolar organiser region (NOR) integrity and function. Immunoprecipitation-based association and colocalization studies demonstrated that HN1 is an important component of the mTOR-RPS6 axis, and its depletion results with reduced mRNA translation in mammalian cancer cell lines. This study also demonstrated that the depletion of HN1 leads to the irregular distribution of nucleolar structures, potentially leading to cell cycle deregulation as reported previously. Accordingly, components of the translation machinery aggregate with a distinct speckled pattern, lose their essential interactions and ultimately impair mRNA translation efficiency when the HN1 is depleted. These results suggest that HN1 is an essential component of the nucleolus, required for ribosome biogenesis as well as global mRNA translation.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13805"},"PeriodicalIF":5.9,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977675","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}
Yu Chen, Peng Wang, Shilin Ma, Chenran Yue, Xupeng Liu, Yeqian Cheng, Kun Liu, Tongbiao Zhao, Ng Shyh-Chang
{"title":"Genetically Engineered Hypoimmune Human Muscle Progenitor Cells Can Reduce Immune Rejection","authors":"Yu Chen, Peng Wang, Shilin Ma, Chenran Yue, Xupeng Liu, Yeqian Cheng, Kun Liu, Tongbiao Zhao, Ng Shyh-Chang","doi":"10.1111/cpr.13802","DOIUrl":"10.1111/cpr.13802","url":null,"abstract":"<p>Cells face two challenges after transplantation: recognition and killing by lymphocytes, and cell apoptosis induced by the transplantation environment. Our hypoimmune cells aim to address these two challenges through editing of immunomodulatory proteins and overexpression of anti-apoptotic proteins.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"58 4","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13802","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945227","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":"Optineurin Cooperates With NRF2 to Regulate Tooth Root Morphogenesis by Controlling Mitochondrial Dynamics and Apoptosis","authors":"Haojie Liu, Xinyu Zhang, Xiao Ge, ChingCho Hsu, Yan Wang, Simai Chen, Xingzhi Yan, Rongyao Xu, Junqing Ma, Shuyu Guo","doi":"10.1111/cpr.13799","DOIUrl":"https://doi.org/10.1111/cpr.13799","url":null,"abstract":"<p>Tooth root development is a complex process essential for tooth function, yet the role of root dentin development in tooth morphogenesis is not fully understood. Optineurin (OPTN), linked to bone disorders like Paget's disease of bone (PDB), may affect tooth root development. In this study, we used single-cell sequencing of embryonic day 16.5 (E16.5), postnatal day 1 (P1), and P7 mouse teeth, as well as embryonic and adult human teeth, to show that OPTN is vital for odontoblastic differentiation. In <i>Optn</i><sup>−/−</sup> mice, we observed short root deformities and defective dentin, with impaired apical papilla differentiation and increased apoptosis. In vitro OPTN downregulation in stem cells of the apical papilla (SCAPs) exacerbated apoptosis and hindered odontoblastic differentiation. RNA-seq analysis revealed significant differences in mitochondrial dynamics between control and OPTN knockout SCAPs. We discovered that OPTN influences mitochondrial dynamics primarily by promoting fission, leading to odontoblastic differentiation and mineralisation. Mechanistically, OPTN cooperates with NRF2 to regulate mitochondrial fission via DRP1 phosphorylation and affects the transcription of <i>BCL2</i>. Rescue experiments using an activator of NRF2 in ex vivo organ cultures and local gingival injection experiments confirmed these findings. Therefore, we concluded that OPTN, interacting with NRF2, acts as a key regulator of SCAPs mitochondrial dynamics, mineralisation and apoptosis during tooth development. These findings provide fresh insights into the mechanisms underlying tooth root development.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"58 5","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13799","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144117821","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}
Xupeng Liu, Ziyue Yao, Liping Zhang, Ng Shyh-Chang
{"title":"Muscle-Derived Bioactive Factors: MyoEVs and Myokines","authors":"Xupeng Liu, Ziyue Yao, Liping Zhang, Ng Shyh-Chang","doi":"10.1111/cpr.13801","DOIUrl":"10.1111/cpr.13801","url":null,"abstract":"<p>Overview of the functions and applications of myokines and MyoEVs.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"58 3","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13801","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906283","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}