Cell Proliferation最新文献

CXCL10 Promotes Spinal Macrophage Recruitment via the JAK/STAT3 Pathway to Induce Pain in Experimental Autoimmune Prostatitis.

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2024-12-24 DOI: 10.1111/cpr.13784

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":"https://doi.org/10.1111/cpr.13784","url":null,"abstract":"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.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13784"},"PeriodicalIF":5.9,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Dual Roles of Lamin A/C in Macrophage Mechanotransduction.

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2024-12-22 DOI: 10.1111/cpr.13794

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":"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.","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}

引用次数: 0

Comparative Analysis of the Therapeutic Potential of Extracellular Vesicles Secreted by Aged and Young Bone Marrow-Derived Mesenchymal Stem Cells in Osteoarthritis Pathogenesis. 老化和年轻骨髓间充质干细胞分泌的细胞外小泡在骨关节炎发病机制中的治疗潜力比较分析》（Comparative Analysis of Therapeutential Extracellular Vesicles Secreted by Aged and Young Bone Marrow-Derived Mesenchymal Stem Cells in Osteoarthritis Pathogenesis）。

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2024-12-20 DOI: 10.1111/cpr.13776

Shital Wakale, Yang Chen, Antonia Rujia Sun, Chamikara Liyanage, Jennifer Gunter, Jyotsna Batra, Ross Crawford, Hongxun Sang, Indira Prasadam

{"title":"Comparative Analysis of the Therapeutic Potential of Extracellular Vesicles Secreted by Aged and Young Bone Marrow-Derived Mesenchymal Stem Cells in Osteoarthritis Pathogenesis.","authors":"Shital Wakale, Yang Chen, Antonia Rujia Sun, Chamikara Liyanage, Jennifer Gunter, Jyotsna Batra, Ross Crawford, Hongxun Sang, Indira Prasadam","doi":"10.1111/cpr.13776","DOIUrl":"https://doi.org/10.1111/cpr.13776","url":null,"abstract":"Osteoarthritis (OA), a joint disease, burdens global healthcare due to aging and obesity. Recent studies show that extracellular vesicles (EVs) from bone marrow-derived mesenchymal stem cells (BMSCs) contribute to joint homeostasis and OA management. However, the impact of donor age on BMSC-derived EV efficacy remains underexplored. In this study, we investigated EV efficacy from young BMSCs (2-month-old) in mitigating OA, contrasting them with EVs from aged BMSCs (27-month-old). The study used destabilisation of the medial meniscus (DMM) surgery on mouse knee joints to induce accelerated OA. Cartilage degeneration markers and senescence markers' expression levels were investigated in response to EV treatment. The therapeutic impact of EVs on chondrocytes under inflammatory responses was also evaluated. Despite having similar morphologies, EVs from young BMSCs markedly decreased senescence and improved chondroprotection by activating the PTEN pathway while simultaneously suppressing the upregulation of the PI3K/AKT pathways, proving to be more effective than those from older BMSCs in vitro. Furthermore, intraperitoneal injections of EVs from young donors significantly mitigated OA progression by preserving cartilage and reducing synovitis in a surgical OA model using DMM in mice. These findings highlight that donor age as a critical determinant in the therapeutic potential of BMSC-derived EVs for clinical use in OA treatment.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13776"},"PeriodicalIF":5.9,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863375","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}

引用次数: 0

Mesenchymal Stem Cell-Derived Exosomes: A Promising Therapeutic Strategy for Age-Related Diseases. 间充质干细胞衍生的外泌体：一种治疗老年性疾病的有效策略

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2024-12-20 DOI: 10.1111/cpr.13795

Bohua Wei, Mengting Wei, Haonan Huang, Ting Fan, Zhichang Zhang, Xiaoyu Song

{"title":"Mesenchymal Stem Cell-Derived Exosomes: A Promising Therapeutic Strategy for Age-Related Diseases.","authors":"Bohua Wei, Mengting Wei, Haonan Huang, Ting Fan, Zhichang Zhang, Xiaoyu Song","doi":"10.1111/cpr.13795","DOIUrl":"https://doi.org/10.1111/cpr.13795","url":null,"abstract":"The global increase in the aging population has led to a concurrent rise in the incidence of age-related diseases, posing substantial challenges to healthcare systems and affecting the well-being of the elderly. Identifying and securing effective treatments has become an urgent priority. In this context, mesenchymal stem cell-derived exosomes (MSC-Exos) have emerged as a promising and innovative modality in the field of anti-aging medicine, offering a multifaceted therapeutic approach. MSC-Exos demonstrate significant potential due to their immunomodulatory and anti-inflammatory properties, their ability to inhibit oxidative stress, and their reparative effects on senescent tissues. These attributes make them valuable in combating a range of conditions associated with aging, such as cardiovascular diseases, neurodegeneration, skin aging, and osteoarthritis. The integration of exosomes with membrane-penetrating peptides introduces a novel strategy for the delivery of biomolecules, surmounting traditional cellular barriers and enhancing therapeutic efficacy. This review provides a comprehensive synthesis of the current understanding of MSC-Exos, underscoring their role as a novel and potent therapeutic strategy against the intricate challenges of age-related diseases.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13795"},"PeriodicalIF":5.9,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863377","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}

引用次数: 0

Investigating Aging-Related Endometrial Dysfunction Using Endometrial Organoids.

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2024-12-18 DOI: 10.1111/cpr.13780

Minghui Lu, Yanli Han, Yu Zhang, Ruijie Yu, Yining Su, Xueyao Chen, Boyang Liu, Tao Li, Rusong Zhao, Han Zhao

{"title":"Investigating Aging-Related Endometrial Dysfunction Using Endometrial Organoids.","authors":"Minghui Lu, Yanli Han, Yu Zhang, Ruijie Yu, Yining Su, Xueyao Chen, Boyang Liu, Tao Li, Rusong Zhao, Han Zhao","doi":"10.1111/cpr.13780","DOIUrl":"https://doi.org/10.1111/cpr.13780","url":null,"abstract":"Ageing of the endometrium is a critical factor that affects reproductive health, yet its intricate mechanisms remain poorly explored. In this study, we performed transcriptome profiling and experimental verification of endometrium and endometrial organoids from young and advanced age females, to elucidate the underlying mechanisms and to explore novel treatment strategies for endometrial ageing. First, we found that age-associated decline in endometrial functions including fibrosis and diminished receptivity, already exists in reproductive age. Subsequently, based on RNA-seq analysis, we identified several changes in molecular processes affected by age, including fibrosis, imbalanced inflammatory status including Th1 bias in secretory phase, cellular senescence and abnormal signalling transduction in key pathways, with all processes been further validated by molecular experiments. Finally, we uncovered for the first time that PI3K-AKT-FOXO1 signalling pathway is overactivated in ageing endometrium and is closely correlated with fibrosis and impaired receptivity characteristics of ageing endometrium. Blocking or activation of PI3K by LY294002 or 740Y-P could attenuate the effect of ageing or accelerate dysfunction of endometrial organoids. This discovery is expected to bring new breakthroughs for understanding the pathophysiological processes associated with endometrial ageing, as well as treatment strategies to improve reproductive outcomes in women of advanced reproductive age.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13780"},"PeriodicalIF":5.9,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853089","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}

引用次数: 0

USP33 Regulates DNA Damage Response and Carcinogenesis Through Deubiquitylating and Stabilising p53.

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2024-12-18 DOI: 10.1111/cpr.13793

Yuqi Zhu, Zixiang Chen, Kaifeng Niu, Mengge Li, Yuchun Deng, Ji Zhang, Di Wei, Jiaqi Wang, YongLiang Zhao

{"title":"USP33 Regulates DNA Damage Response and Carcinogenesis Through Deubiquitylating and Stabilising p53.","authors":"Yuqi Zhu, Zixiang Chen, Kaifeng Niu, Mengge Li, Yuchun Deng, Ji Zhang, Di Wei, Jiaqi Wang, YongLiang Zhao","doi":"10.1111/cpr.13793","DOIUrl":"https://doi.org/10.1111/cpr.13793","url":null,"abstract":"The de-ubiquitinase USP33 has been shown to possess either tumour-promoting or inhibitory effect on human cancer cells. However, all these findings are mainly based on in vitro cell culture models, and the in vivo evidence, which is more plausible to digest the functional role of USP33 in carcinogenic process, is still lacking. Here, we demonstrate that USP33 modulates DNA damage responses including cell cycle arrest and apoptosis induction through associating with p53. It directly interacts with p53 to mediate its de-ubiquitination and further stabilisation under DNA damage condition. Depletion of USP33 induces an enhanced level of p53 ubiquitination, which de-stabilises p53 protein leading to impaired DNA damage responses. Furthermore, USP33 silencing shows either promoted or inhibited effect on cell proliferation in human cancer cells with p53 WT and mutant background, respectively. Consistently, mice with hepatocyte-specific USP33 knockout are more sensitive to nitrosodiethylamine (DEN)-induced hepatocarcinogenesis compared to wild type mice. Thus, our in vitro and in vivo evidences illustrate that USP33 possesses anti-tumour activity via regulating p53 stability and activity.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13793"},"PeriodicalIF":5.9,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853092","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}

引用次数: 0

CTCF Point Mutation at R567 Disrupts Mouse Heart Development via 3D Genome Rearrangement and Transcription Dysregulation.

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2024-12-16 DOI: 10.1111/cpr.13783

Huawei Ren, Hongxin Zhong, Jie Zhang, Yuli Lu, Gongcheng Hu, Weixun Duan, Ning Ma, Hongjie Yao

{"title":"CTCF Point Mutation at R567 Disrupts Mouse Heart Development via 3D Genome Rearrangement and Transcription Dysregulation.","authors":"Huawei Ren, Hongxin Zhong, Jie Zhang, Yuli Lu, Gongcheng Hu, Weixun Duan, Ning Ma, Hongjie Yao","doi":"10.1111/cpr.13783","DOIUrl":"https://doi.org/10.1111/cpr.13783","url":null,"abstract":"CTCF plays a vital role in shaping chromatin structure and regulating gene expression. Clinical studies have associated CTCF mutations with congenital developmental abnormalities, including congenital cardiomyopathy. In this study, we investigated the impact of the homozygous CTCF-R567W (CtcfR567W/R567W) mutation on cardiac tissue morphogenesis during mouse embryonic development. Our results reveal significant impairments in heart development, characterised by ventricular muscle trabecular hyperplasia and reduced ventricular cavity sizes. We also observe a marked downregulation of genes involved in sarcomere assembly, calcium ion transport, and mitochondrial function in heart tissues from homozygous mice. Furthermore, the CtcfR567W/R567W mutation disrupts CTCF's interaction with chromatin, resulting in alterations to topologically associating domain (TAD) structure within specific genomic regions and diminishing crucial promoter-enhancer interactions necessary for cardiac development. Additionally, we find that the heterozygous CTCF-R567W (Ctcf+/R567W) mutation significantly compromises cardiac contractility in 8-week-old mice. This study elucidates the mechanism by which the CTCF-R567W mutation hampers cardiac development, underscoring the essential role of CTCF-R567 in embryonic heart development and maturation.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13783"},"PeriodicalIF":5.9,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834268","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}

引用次数: 0

Implication of GPRASP2 in the Proliferation and Hair Cell-Forming of Cochlear Supporting Cells. GPRASP2 对耳蜗支持细胞增殖和毛细胞形成的影响

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2024-12-15 DOI: 10.1111/cpr.13792

Jing Cai, Kun Huang, Wenrui Li, Tianming Wang, Shen Yue, Zhibin Chen, Guangqian Xing, Qinjun Wei, Jun Yao, Xin Cao

引用次数: 0

Single-Cell Multiomics Reveals TCR Clonotype-Specific Phenotype and Stemness Heterogeneity of T-ALL Cells. 单细胞多组学揭示 TCR 克隆型特异性表型和 T-ALL 细胞的干性异质性

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2024-12-15 DOI: 10.1111/cpr.13786

Songnan Sui, Xiaolei Wei, Yue Zhu, Qiuyue Feng, Xianfeng Zha, Lipeng Mao, Boya Huang, Wen Lei, Guobing Chen, Huien Zhan, Huan Chen, Ru Feng, Chengwu Zeng, Yangqiu Li, Oscar Junhong Luo

{"title":"Single-Cell Multiomics Reveals TCR Clonotype-Specific Phenotype and Stemness Heterogeneity of T-ALL Cells.","authors":"Songnan Sui, Xiaolei Wei, Yue Zhu, Qiuyue Feng, Xianfeng Zha, Lipeng Mao, Boya Huang, Wen Lei, Guobing Chen, Huien Zhan, Huan Chen, Ru Feng, Chengwu Zeng, Yangqiu Li, Oscar Junhong Luo","doi":"10.1111/cpr.13786","DOIUrl":"https://doi.org/10.1111/cpr.13786","url":null,"abstract":"T-cell acute lymphoblastic leukaemia (T-ALL) is a heterogeneous malignant disease with high relapse and mortality rates. To characterise the multiomics features of T-ALL, we conducted integrative analyses using single-cell RNA, TCR and chromatin accessibility sequencing on pre- and post-treatment peripheral blood and bone marrow samples of the same patients. We found that there is transcriptional rewiring of gene regulatory networks in T-ALL cells. Some transcription factors, such as TCF3 and KLF3, showed differences in activity and expression levels between T-ALL and normal T cells and were associated with the prognosis of T-ALL patients. Furthermore, we identified multiple malignant TCR clonotypes among the T-ALL cells, where the clonotypes consisted of distinct combinations of the same TCR α and β chain per patient. The T-ALL cells displayed clonotype-specific immature thymocyte cellular characteristics and response to chemotherapy. Remarkably, T-ALL cells with an orphan TCRβ chain displayed the strongest stemness and resistance to chemotherapy. Our study provided transcriptome and epigenome characterisation of T-ALL cells categorised by TCR clonotypes, which may be helpful for the development of novel predictive markers to evaluate treatment effectiveness for T-ALL.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13786"},"PeriodicalIF":5.9,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827565","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}

引用次数: 0

Conditional Overexpression of Net1 Enhances the Trans-Differentiation of Lgr5⁺ Progenitors into Hair Cells in the Neonatal Mouse Cochlea. 条件性过表达 Net1 可增强新生小鼠耳蜗中 Lgr5+祖细胞向毛细胞的转分化。

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2024-12-15 DOI: 10.1111/cpr.13787

Yanqin Lin, Qiuyue Zhang, Wei Tong, Yintao Wang, Leilei Wu, Hairong Xiao, Xujun Tang, Mingchen Dai, Zixuan Ye, Renjie Chai, Shasha Zhang

{"title":"Conditional Overexpression of Net1 Enhances the Trans-Differentiation of Lgr5+ Progenitors into Hair Cells in the Neonatal Mouse Cochlea.","authors":"Yanqin Lin, Qiuyue Zhang, Wei Tong, Yintao Wang, Leilei Wu, Hairong Xiao, Xujun Tang, Mingchen Dai, Zixuan Ye, Renjie Chai, Shasha Zhang","doi":"10.1111/cpr.13787","DOIUrl":"https://doi.org/10.1111/cpr.13787","url":null,"abstract":"Sensorineural hearing loss is mainly caused by damage to hair cells (HC), which cannot be regenerated spontaneously in adult mammals once damaged. Cochlear Lgr5+ progenitors are characterised by HC regeneration capacity in neonatal mice, and we previously screened several new genes that might induce HC regeneration from Lgr5+ progenitors. Net1, a guanine nucleotide exchange factor, is one of the screened new genes and is particularly active in cancer cells and is involved in cell proliferation and differentiation. Here, to explore in vivo roles of Net1 in HC regeneration, Net1loxp/loxp mice were constructed and crossed with Lgr5CreER/+ mice to conditionally overexpress (cOE) Net1 in cochlear Lgr5+ progenitors. We observed a large number of ectopic HCs in Lgr5CreER/+Net1loxp/loxp mouse cochlea, which showed a dose-dependent effect. Moreover, the EdU assay was unable to detect any EdU+/Sox2+ supporting cells, while lineage tracing showed significantly more regenerated tdTomato+ HCs in Lgr5CreER/+Net1loxp/loxptdTomato mice, which indicated that Net1 cOE enhanced HC regeneration by inducing the direct trans-differentiation of Lgr5+ progenitors rather than mitotic HC regeneration. Additionally, qPCR results showed that the transcription factors related to HC regeneration, including Atoh1, Gfi1 and Pou4f3, were significantly upregulated and are probably the mechanism behind the HC regeneration induced by Net1. In conclusion, our study provides new evidence for the role of Net1 in enhancing HC regeneration in the neonatal mouse cochlea.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13787"},"PeriodicalIF":5.9,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827563","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}

引用次数: 0