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}
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}
Weijie Xu, Qiuru Huang, Yujuan Qi, Qingqing Hu, Cong Shen, Xia Chen, Jiaxin Li, Qiushi Xia, Ziyue Pan, Yi Zhang, Guoqing Han, Jingqi Huang, Yiheng Liu, Ziyu Cao, Ying Zheng, Bo Zheng, Zhifeng Gu, Jun Yu, Chi Sun
{"title":"Single-Cell Transcriptomics Uncovers Core Signature for Regulating Mitochondrial Homeostasis During Testicular Ageing.","authors":"Weijie Xu, Qiuru Huang, Yujuan Qi, Qingqing Hu, Cong Shen, Xia Chen, Jiaxin Li, Qiushi Xia, Ziyue Pan, Yi Zhang, Guoqing Han, Jingqi Huang, Yiheng Liu, Ziyu Cao, Ying Zheng, Bo Zheng, Zhifeng Gu, Jun Yu, Chi Sun","doi":"10.1111/cpr.13797","DOIUrl":"https://doi.org/10.1111/cpr.13797","url":null,"abstract":"<p><p>Testicular ageing is accompanied by a series of morphological changes, while the features of mitochondrial dysfunction remain largely unknown. Herein, we observed a range of age-related modifications in testicular morphology and spermatogenic cells, and conducted single-cell RNA sequencing on young and old testes in Drosophila. Pseudotime trajectory revealed significant changes in germline subpopulations during ageing. Our examination unveiled that genes showing bias in spermatids exhibited higher dN/dS than those in GSCs_Spermatogonia. Genes biased towards young GSCs_Spermatogonia displayed higher dN/dS than those in old GSCs_Spermatogonia. Interestingly, genes biased towards young spermatids demonstrated lower dN/dS in contrast to those in old spermatids, revealing the complexity of evolutionary adaptations during ageing. Furthermore, mitochondria associated events, including oxidative phosphorylation, TCA cycle and pyruvate metabolism, were significantly enriched in germline subpopulations. Specifically, mitochondrial function was significantly impaired during the process of testicular ageing, concurrently emphasising the role of several key nuclear genome-encoded mitochondrial regulatory genes, such as Hsp60B, fzo, Tim17b1 and mRpL12. Our data offer insights into testicular homeostasis regulated by mitochondrial function during the ageing process.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13797"},"PeriodicalIF":5.9,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892439","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":"Revolutionising Cancer Immunotherapy: Advancements and Prospects in Non-Viral CAR-NK Cell Engineering","authors":"Zhaokai Zhou, Yifeng Chen, Yuhao Ba, Hui Xu, Anning Zuo, Shutong Liu, Yuyuan Zhang, Siyuan Weng, Yuqing Ren, Peng Luo, Quan Cheng, Lulu Zuo, Shanshan Zhu, Xing Zhou, Chuhan Zhang, Yukang Chen, Xinwei Han, Teng Pan, Zaoqu Liu","doi":"10.1111/cpr.13791","DOIUrl":"10.1111/cpr.13791","url":null,"abstract":"<p>The recent advancements in cancer immunotherapy have spotlighted the potential of natural killer (NK) cells, particularly chimeric antigen receptor (CAR)–transduced NK cells. These cells, pivotal in innate immunity, offer a rapid and potent response against cancer cells and pathogens without the need for prior sensitization or recognition of peptide antigens. Although NK cell genetic modification is evolving, the viral transduction method continues to be inefficient and fraught with risks, often resulting in cytotoxic outcomes and the possibility of insertional mutagenesis. Consequently, there has been a surge in the development of non-viral transfection technologies to overcome these challenges in NK cell engineering. Non-viral approaches for CAR-NK cell generation are becoming increasingly essential. Cutting-edge techniques such as trogocytosis, electroporation, lipid nanoparticle (LNP) delivery, clustered regularly interspaced short palindromic repeats–associated protein 9 (CRISPR-Cas9) gene editing and transposons not only enhance the efficiency and safety of CAR-NK cell engineering but also open new avenues for novel therapeutic possibilities. Additionally, the infusion of technologies already successful in CAR T-cell therapy into the CAR-NK paradigm holds immense potential for further advancements. In this review, we present an overview of the potential of NK cells in cancer immunotherapies, as well as non-viral transfection technologies for engineering NK cells.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"58 4","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13791","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892438","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":"Mitonuclear Communication in Stem Cell Function.","authors":"Baozhou Peng, Yaning Wang, Hongbo Zhang","doi":"10.1111/cpr.13796","DOIUrl":"https://doi.org/10.1111/cpr.13796","url":null,"abstract":"<p><p>Mitochondria perform multiple functions within the cell, including the production of ATP and a great deal of metabolic intermediates, while also contributing to the cellular stress response. The majority of mitochondrial proteins are encoded by nuclear genomes, highlighting the importance of mitonuclear communication for sustaining mitochondrial homeostasis and functional. As a crucial part of the intracellular signalling network, mitochondria can impact stem cell fate determinations. Considering the essential function of stem cells in tissue maintenance, regeneration and aging, it is important to understand how mitochondria influence stem cell fate. This review explores the significant roles of mitonuclear communication and mitochondrial proteostasis, highlighting their influence on stem cells. We also examine how mitonuclear interactions contribute to cellular homeostasis, stem cell therapies, and the potential for extending lifespan.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13796"},"PeriodicalIF":5.9,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892430","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}
Lei Chen, Ziqi Chen, Jia Chen, Hexi Du, Xianguo Chen, Jing Chen, Hui Wang, Chaozhao Liang
{"title":"CXCL10 Promotes Spinal Macrophage Recruitment via the JAK/STAT3 Pathway to Induce Pain in Experimental Autoimmune Prostatitis","authors":"Lei Chen, Ziqi Chen, Jia Chen, Hexi Du, Xianguo Chen, Jing Chen, Hui Wang, Chaozhao Liang","doi":"10.1111/cpr.13784","DOIUrl":"10.1111/cpr.13784","url":null,"abstract":"<p>The aim is to explore the mechanisms underlying pain development in chronic prostatitis and identify therapeutic targets for pain management in patients with chronic prostatitis. RNA sequence of the spinal cord dorsal horns and proteomic analysis of spinal macrophages of experimental autoimmune prostatitis (EAP) mice were conducted to identify pain-related genes, proteins and signalling pathways. The clodronate liposome, CXCR3 and P-STAT3 inhibitors, NGF antibody and cromolyn sodium were used to investigate the roles of the CXCL10/CXCR3, JAK/STAT3 and NGF/TrKA pathways in spinal macrophage recruitment and pain response. Finally, prostate tissues from benign prostate hyperplasia (BPH) patients were collected to validate the aforementioned results. Neuron and astrocyte-derived CXCL10 was associated with spinal macrophage recruitment, and CXCL10/CXCR3 axis could regulate the chemotaxis of macrophage to the spinal cord in EAP mice. Results of proteomic analysis found that CXCL10 could regulate the JAK/STAT3 pathway to mediate neuroinflammation in EAP, which was validated in vivo and in vitro experiments. The number of mast cells and expressions of NGF, TrKA and PGP9.5 increased in the prostates of EAP mice and BPH patients, and targeting NGF could reduce spinal macrophage recruitment and pain response. NGF was the triggering factor to induce chemotaxis of spinal macrophages and neuroinflammation, and the CXCL10/CXCR3 axis and JAK/STAT3 pathway was involved in spinal macrophage recruitment and infiltration, which provided therapeutic targets for pain management.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"58 4","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13784","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884976","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}
Yao Wang, Sabine Ruf, Lei Wang, Thomas Heimerl, Gert Bange, Sabine Groeger
{"title":"The Dual Roles of Lamin A/C in Macrophage Mechanotransduction.","authors":"Yao Wang, Sabine Ruf, Lei Wang, Thomas Heimerl, Gert Bange, Sabine Groeger","doi":"10.1111/cpr.13794","DOIUrl":"https://doi.org/10.1111/cpr.13794","url":null,"abstract":"<p><p>Cellular mechanotransduction is a complex physiological process that integrates alterations in the external environment with cellular behaviours. In recent years, the role of the nucleus in mechanotransduction has gathered increased attention. Our research investigated the involvement of lamin A/C, a component of the nuclear envelope, in the mechanotransduction of macrophages under compressive force. We discovered that hydrostatic compressive force induces heterochromatin formation, decreases SUN1/SUN2 levels, and transiently downregulates lamin A/C. Notably, downregulated lamin A/C increased nuclear permeability to yes-associated protein 1 (YAP1), thereby amplifying certain effects of force, such as inflammation induction and proliferation inhibition. Additionally, lamin A/C deficiency detached the linker of nucleoskeleton and cytoskeleton (LINC) complex from nuclear envelope, consequently reducing force-induced DNA damage and IRF4 expression. In summary, lamin A/C exerted dual effects on macrophage responses to mechanical compression, promoting certain outcomes while inhibiting others. It operated through two distinct mechanisms: enhancing nuclear permeability and impairing intracellular mechanotransmission. The results of this study support the understanding of the mechanisms of intracellular mechanotransduction and may assist in identifying potential therapeutic targets for mechanotransduction-related diseases.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13794"},"PeriodicalIF":5.9,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876290","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}