Cell Proliferation最新文献

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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,&nbsp;Qiuyue Zhang,&nbsp;Wei Tong,&nbsp;Yintao Wang,&nbsp;Leilei Wu,&nbsp;Hairong Xiao,&nbsp;Xujun Tang,&nbsp;Mingchen Dai,&nbsp;Zixuan Ye,&nbsp;Renjie Chai,&nbsp;Shasha Zhang","doi":"10.1111/cpr.13787","DOIUrl":"10.1111/cpr.13787","url":null,"abstract":"<p>Sensorineural hearing loss is mainly caused by damage to hair cells (HC), which cannot be regenerated spontaneously in adult mammals once damaged. Cochlear Lgr5<sup>+</sup> progenitors are characterised by HC regeneration capacity in neonatal mice, and we previously screened several new genes that might induce HC regeneration from Lgr5<sup>+</sup> progenitors. <i>Net1</i>, 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, <i>Net1</i>\u0000 <sup>\u0000 <i>loxp/loxp</i>\u0000 </sup> mice were constructed and crossed with <i>Lgr5</i>\u0000 <sup>\u0000 <i>CreER/+</i>\u0000 </sup> mice to conditionally overexpress (cOE) <i>Net1</i> in cochlear Lgr5<sup>+</sup> progenitors. We observed a large number of ectopic HCs in <i>Lgr5</i>\u0000 <sup>\u0000 <i>CreER/+</i>\u0000 </sup>\u0000 <i>Net1</i>\u0000 <sup>\u0000 <i>loxp/loxp</i>\u0000 </sup> mouse cochlea, which showed a dose-dependent effect. Moreover, the EdU assay was unable to detect any EdU<sup>+</sup>/Sox2<sup>+</sup> supporting cells, while lineage tracing showed significantly more regenerated tdTomato<sup>+</sup> HCs in <i>Lgr5</i>\u0000 <sup>\u0000 <i>CreER/+</i>\u0000 </sup>\u0000 <i>Net1</i>\u0000 <sup>\u0000 <i>loxp/loxp</i>\u0000 </sup>\u0000 <i>tdTomato</i> mice, which indicated that <i>Net1</i> cOE enhanced HC regeneration by inducing the direct trans-differentiation of Lgr5<sup>+</sup> progenitors rather than mitotic HC regeneration. Additionally, qPCR results showed that the transcription factors related to HC regeneration, including <i>Atoh1</i>, <i>Gfi1</i> and <i>Pou4f3</i>, were significantly upregulated and are probably the mechanism behind the HC regeneration induced by <i>Net1</i>. In conclusion, our study provides new evidence for the role of <i>Net1</i> in enhancing HC regeneration in the neonatal mouse cochlea.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"58 4","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13787","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Human Brain Organoids Model Abnormal Prenatal Neural Development Induced by Thermal Stimulation 热刺激诱导胎儿神经发育异常的人脑类器官模型。
IF 5.9 1区 生物学
Cell Proliferation Pub Date : 2024-12-12 DOI: 10.1111/cpr.13777
Lei Xu, Yufan Zhang, Xingyi Chen, Yuan Hong, Xu Zhang, Hao Hu, Xiao Han, Xiao Zou, Min Xu, Wanying Zhu, Yan Liu
{"title":"Human Brain Organoids Model Abnormal Prenatal Neural Development Induced by Thermal Stimulation","authors":"Lei Xu,&nbsp;Yufan Zhang,&nbsp;Xingyi Chen,&nbsp;Yuan Hong,&nbsp;Xu Zhang,&nbsp;Hao Hu,&nbsp;Xiao Han,&nbsp;Xiao Zou,&nbsp;Min Xu,&nbsp;Wanying Zhu,&nbsp;Yan Liu","doi":"10.1111/cpr.13777","DOIUrl":"10.1111/cpr.13777","url":null,"abstract":"<p>The developing human foetal brain is sensitive to thermal stimulation during pregnancy. However, the mechanisms by which heat exposure affects human foetal brain development remain unclear, largely due to the lack of appropriate research models for studying thermal stimulation. To address this, we have developed a periodic heating model based on brain organoids derived from human pluripotent stem cells. The model recapitulated neurodevelopmental disruptions under prenatal heat exposure at the early stages, providing a paradigm for studying the altered neurodevelopment under environmental stimulation. Our study found that periodic heat exposure led to decreased size and impaired neural tube development in the brain organoids. Bulk RNA-seq analysis revealed that the abnormal WNT signalling pathway and the reduction of G2/M progenitor cells might be involved in heat stimulation. Further investigation revealed increased neural differentiation and decreased proliferation under heat stimulation, indicating that periodic heat exposure might lead to abnormal brain development by altering key developmental processes. Hence, our model of periodically heating brain organoids provides a platform for modelling the effects of maternal fever on foetal brain development and could be extended to applications in neurodevelopmental disorders intervention.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"58 2","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13777","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817266","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}
引用次数: 0
A Chemical Reprogramming Approach Efficiently Producing Human Retinal Pigment Epithelium Cells for Retinal Disease Therapies. 一种化学重编程方法有效地产生用于视网膜疾病治疗的人视网膜色素上皮细胞。
IF 5.9 1区 生物学
Cell Proliferation Pub Date : 2024-12-12 DOI: 10.1111/cpr.13785
Ke Zhang, Yanqiu Wang, Qi An, Hengjing Ji, Defu Wu, Xuri Li, Lingge Suo, Chun Zhang, Xuran Dong
{"title":"A Chemical Reprogramming Approach Efficiently Producing Human Retinal Pigment Epithelium Cells for Retinal Disease Therapies.","authors":"Ke Zhang, Yanqiu Wang, Qi An, Hengjing Ji, Defu Wu, Xuri Li, Lingge Suo, Chun Zhang, Xuran Dong","doi":"10.1111/cpr.13785","DOIUrl":"https://doi.org/10.1111/cpr.13785","url":null,"abstract":"<p><p>Human induced pluripotent stem cells (hiPSCs) represent a promising cell source for generating functional cells suitable for clinical therapeutic applications, particularly in the context of autologous cell therapies. However, the production of hiPSCs through genetic manipulation, especially involving oncogenes, may raise safety concerns. Furthermore, the complexity and high costs associated with hiPSCs generation have hindered their broad clinical use. In this study, we utilised a recently developed chemical reprogramming method in conjunction with a guided differentiation protocol, introducing a chemically defined strategy for generating functional human retinal pigment epithelium (RPE) cells from adipose tissue, bypassing conventional hiPSCs generation challenges. By utilising small molecule-based chemical cocktails, we reprogrammed somatic adipose cells into human chemically induced pluripotent stem cells (hCiPSCs) in a safer and more streamlined manner, entirely free from gene manipulation. Subsequent differentiation of hCiPSCs into functional RPE cells demonstrated their capability for secretion and phagocytosis, emphasising their vital role in maintaining retinal homeostasis and underscoring their therapeutic potential. Our findings highlight the transformative potential of hCiPSCs as a safer, more efficient option for personalised cell therapies, with applications extending beyond ocular disease to a wide range of medical conditions.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13785"},"PeriodicalIF":5.9,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817261","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
Scutellarin Alleviates Bone Marrow Mesenchymal Stromal Cellular Senescence via the Ezh2-Nrf2 Signalling Axis in Diabetes-Induced Bone Loss 黄芩素通过Ezh2-Nrf2信号轴在糖尿病诱导的骨质流失中缓解骨髓间充质细胞衰老
IF 5.9 1区 生物学
Cell Proliferation Pub Date : 2024-12-12 DOI: 10.1111/cpr.13790
Tiantian Wang, Jiehao Chen, Bo Qu, Dong Zhou, Zhen Hong
{"title":"Scutellarin Alleviates Bone Marrow Mesenchymal Stromal Cellular Senescence via the Ezh2-Nrf2 Signalling Axis in Diabetes-Induced Bone Loss","authors":"Tiantian Wang,&nbsp;Jiehao Chen,&nbsp;Bo Qu,&nbsp;Dong Zhou,&nbsp;Zhen Hong","doi":"10.1111/cpr.13790","DOIUrl":"10.1111/cpr.13790","url":null,"abstract":"<p>Currently, there is no specific treatment for diabetes-induced osteoporosis (DOP). Our study identified diabetes-induced cellular senescence, marked by elevated activity of senescence-associated β-galactosidase. Targeting senescent cells holds promise for osteoporosis treatment. We demonstrated that scutellarin (SCU) effectively mitigated bone loss in DOP mice, and co-treatment with SCU significantly reduced diabetes-induced senescence in LepR+MSCs. Furthermore, our research highlighted the role of Nrf2 in SCU's anti-senescence effects on bone. The deletion of Nrf2 impaired SCU's ability to alleviate DOP. Mechanistically, SCU enhances Ezh2 expression and increases H3K27me3 activity at the Keap1 promoter region, leading to Keap1 repression and enhanced Nrf2-ARE signalling. Additionally, SCU notably inhibited cellular senescence and diabetes-related osteoporosis, these effects were significantly reduced in Ezh2<sup>LepRcre</sup> conditional knockout models. These findings suggest that the Ezh2-Nrf2 signalling axis is crucial for mediating SCU's beneficial effects in this context. Overall, our discoveries provide insights into the mechanisms underlying DOP and propose a potential preventive strategy for this condition.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"58 4","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13790","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817278","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}
引用次数: 0
Featured Cover 精选封面
IF 5.9 1区 生物学
Cell Proliferation Pub Date : 2024-12-09 DOI: 10.1111/cpr.13789
Yao Yao, Xin Bin, Yanxuan Xu, Shaowan Chen, Si Chen, Xiang-Ling Yuan, Yingjie Cao, Tsz Kin Ng
{"title":"Featured Cover","authors":"Yao Yao,&nbsp;Xin Bin,&nbsp;Yanxuan Xu,&nbsp;Shaowan Chen,&nbsp;Si Chen,&nbsp;Xiang-Ling Yuan,&nbsp;Yingjie Cao,&nbsp;Tsz Kin Ng","doi":"10.1111/cpr.13789","DOIUrl":"https://doi.org/10.1111/cpr.13789","url":null,"abstract":"<p>The cover image is based on the article <i>Cellular senescence mediates retinal ganglion cell survival regulation post-optic nerve crush injury</i> by Yao Yao et al., https://doi.org/10.1111/cpr.13719.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"57 12","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13789","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142868323","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}
引用次数: 0
Multi-omics revealed that DCP1A and SPDL1 determine embryogenesis defects in postovulatory ageing oocytes 多组学发现DCP1A和SPDL1决定排卵后老化卵母细胞的胚胎发生缺陷。
IF 5.9 1区 生物学
Cell Proliferation Pub Date : 2024-12-04 DOI: 10.1111/cpr.13766
Li Kong, Yutian Gong, Yongyong Wang, Mengjiao Yuan, Wenxiang Liu, Heyang Zhou, Xiangyue Meng, Xinru Guo, Yongbin Liu, Yang Zhou, Teng Zhang
{"title":"Multi-omics revealed that DCP1A and SPDL1 determine embryogenesis defects in postovulatory ageing oocytes","authors":"Li Kong,&nbsp;Yutian Gong,&nbsp;Yongyong Wang,&nbsp;Mengjiao Yuan,&nbsp;Wenxiang Liu,&nbsp;Heyang Zhou,&nbsp;Xiangyue Meng,&nbsp;Xinru Guo,&nbsp;Yongbin Liu,&nbsp;Yang Zhou,&nbsp;Teng Zhang","doi":"10.1111/cpr.13766","DOIUrl":"10.1111/cpr.13766","url":null,"abstract":"<p>Growing evidence indicates that the deterioration of egg quality caused by postovulatory ageing significantly hampers embryonic development. However, the molecular mechanisms by which postovulatory ageing leads to a decline in oocyte quality have not been fully characterized. In this study, we observed an accelerated decay of maternal mRNAs through RNA-seq analyses in postovulatory-aged (PostOA) oocytes. We noted that these downregulated mRNAs should be degraded during the 2-cell stage. Proteomic analyses revealed that the degradation of maternal mRNAs is associated with the accumulation of DCP1A. The injection of exogenous <i>Dcp1a</i> mRNA or siRNA into MII stage oocytes proved that DCP1A could accelerate the degradation of maternal mRNAs. Additionally, we also found that SPDL1 is crucial for maintaining spindle/chromosome structure and chromosome euploidy in PostOA oocytes. <i>Spdl1-</i>mRNA injection remarkably recovered the meiotic defects in PostOA oocytes. Collectively, our findings provide valuable insights into the molecular mechanisms underlying postovulatory ageing.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"58 3","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13766","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766614","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}
引用次数: 0
Ferroptosis in Osteoarthritis: Towards Novel Therapeutic Strategy 骨关节炎的上睑下垂:迈向新的治疗策略。
IF 5.9 1区 生物学
Cell Proliferation Pub Date : 2024-12-03 DOI: 10.1111/cpr.13779
Yiming Zhang, Jing Li, Jiane Liu, Yan Gao, Kehan Li, Xinyu Zhao, Yufeng Liu, Daijie Wang, Xiao Hu, Zheng Wang
{"title":"Ferroptosis in Osteoarthritis: Towards Novel Therapeutic Strategy","authors":"Yiming Zhang,&nbsp;Jing Li,&nbsp;Jiane Liu,&nbsp;Yan Gao,&nbsp;Kehan Li,&nbsp;Xinyu Zhao,&nbsp;Yufeng Liu,&nbsp;Daijie Wang,&nbsp;Xiao Hu,&nbsp;Zheng Wang","doi":"10.1111/cpr.13779","DOIUrl":"10.1111/cpr.13779","url":null,"abstract":"<p>Osteoarthritis (OA) is a chronic, degenerative joint disease primarily characterised by damage to the articular cartilage, synovitis and persistent pain, and has become one of the most common diseases worldwide. In OA cartilage, various forms of cell death have been identified, including apoptosis, necroptosis and autophagic cell death. Ever-growing observations indicate that ferroptosis, a newly-discovered iron-dependent form of regulated cell death, is detrimental to OA occurrence and progression. In this review, we first analyse the pathogenetic mechanisms of OA by which iron overload, inflammatory response and mechanical stress contribute to ferroptosis. We then discuss how ferroptosis exacerbates OA progression, focusing on its impact on chondrocyte viability, synoviocyte populations and extracellular matrix integrity. Finally, we highlight several potential therapeutic strategies targeting ferroptosis that could be explored for the treatment of OA.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"58 3","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13779","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766613","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}
引用次数: 0
Ubiquitin-Proteasome System in Periodontitis: Mechanisms and Clinical Implications 牙周炎的泛素-蛋白酶体系统:机制和临床意义。
IF 5.9 1区 生物学
Cell Proliferation Pub Date : 2024-12-03 DOI: 10.1111/cpr.13781
Yilin Ma, Ruiwei Jia, Shuhong Chen, Jun Ma, Lei Yin, Xingbei Pan, Yunuo He, Tong Wu, Zheyu Zhao, Lulu Ma, Shengzhuang Wu, Huining Wang, Guang Liang, Shengbin Huang, Xiaoyu Sun
{"title":"Ubiquitin-Proteasome System in Periodontitis: Mechanisms and Clinical Implications","authors":"Yilin Ma,&nbsp;Ruiwei Jia,&nbsp;Shuhong Chen,&nbsp;Jun Ma,&nbsp;Lei Yin,&nbsp;Xingbei Pan,&nbsp;Yunuo He,&nbsp;Tong Wu,&nbsp;Zheyu Zhao,&nbsp;Lulu Ma,&nbsp;Shengzhuang Wu,&nbsp;Huining Wang,&nbsp;Guang Liang,&nbsp;Shengbin Huang,&nbsp;Xiaoyu Sun","doi":"10.1111/cpr.13781","DOIUrl":"10.1111/cpr.13781","url":null,"abstract":"<p>The progression of periodontitis, a bacteria-driven inflammatory and bone-destructive disease, involves myriad cellular and molecular mechanisms. Protein regulation significantly influences the pathogenesis and management of periodontitis. However, research regarding its regulatory role in periodontitis remains relatively limited. The ubiquitin-proteasome system (UPS), which mainly involves ubiquitination by E3 ubiquitin ligases (E3s) and deubiquitination by deubiquitinating enzymes (DUBs), is the primary intracellular and non-lysosomal mechanism of protein degradation. Recent studies have provided compelling evidence to support the involvement of UPS in periodontitis progression. Increasing evidence indicated that E3s, such as CUL3, Nedd4-2, Synoviolin, FBXL19, PDLIM2, TRIMs and TRAFs, modulate inflammatory responses and bone resorption in periodontitis through multiple classical signalling pathways, including NLRP3, GSDMD, NF-κB, Wnt/β-catenin and Nrf2. Meanwhile, DUBs, including OTUD1, A20, CYLD, UCH-L1 and USPs, also broadly modulate periodontitis progression by regulating signalling pathways such as NF-κB, Wnt/β-catenin, NLRP3, and BMP2. Therefore, the modulation of E3s and DUBs has proven to be an effective therapy against periodontitis. This review provides a comprehensive overview of the regulatory role of ubiquitinating and deubiquitinating enzymes in periodontitis progression and the underlying mechanisms. Finally, we summarise several chemical and genetic methods that regulate UPS enzymes and pave the way for the development of targeted therapies for periodontitis.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"58 3","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13781","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766615","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}
引用次数: 0
METTL16 and YTHDC1 Regulate Spermatogonial Differentiation via m6A. METTL16和YTHDC1通过m6A调控精原细胞分化。
IF 5.9 1区 生物学
Cell Proliferation Pub Date : 2024-11-29 DOI: 10.1111/cpr.13782
Xueying Gu, Xinyuan Dai, Haifeng Sun, Yilong Lian, Xingxu Huang, Bin Shen, Pengfei Zhang
{"title":"METTL16 and YTHDC1 Regulate Spermatogonial Differentiation via m6A.","authors":"Xueying Gu, Xinyuan Dai, Haifeng Sun, Yilong Lian, Xingxu Huang, Bin Shen, Pengfei Zhang","doi":"10.1111/cpr.13782","DOIUrl":"https://doi.org/10.1111/cpr.13782","url":null,"abstract":"<p><p>Spermatogenesis is a highly unique and intricate process, finely regulated at multiple levels, including post-transcriptional regulation. N6-methyladenosine (m6A), the most prevalent internal modification in eukaryotic mRNA, plays a significant role in transcriptional regulation during spermatogenesis. Previous research indicated extensive m6A modification at each stage of spermatogenesis, but depletion of Mettl3 and/or Mettl14 in spermatogenic cells with Stra8-Cre did not reveal any detectable abnormalities up to the stage of elongating spermatids. This suggests the involvement of other methyltransferases in the regulation of m6A modification during spermatogonial differentiation and meiosis. As a METTL3/14-independent m6A methyltransferase, METTL16 remains insufficiently studied in its roles during spermatogenesis. We report that male mice with Mettl16<sup>vasa-cre</sup> exhibited significantly smaller testes, accompanied by a progressive loss of spermatogonia after birth. Additionally, the deletion of Mettl16 in A1 spermatogonia using Stra8-Cre results in a blockade in spermatogonial differentiation. Given YTHDC1's specific recognition for METTL16 target genes, we further investigated the role of YTHDC1 using Ythdc1-sKO mouse model. Our results indicate that Ythdc1<sup>Stra8-cre</sup> also impairs spermatogonial differentiation, similar to the effects observed in Mettl16<sup>Stra8-cre</sup> mice. RNA-seq and m6A-seq analyses revealed that deletion of either Mettl6 or Ythdc1 disrupted the gene expression related to chromosome organisation and segregation, ultimately leading to male infertility. Collectively, this study underscores the essential roles of the m6A writer METTL16 and its reader YTHDC1 in the differentiation of spermatogonia.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13782"},"PeriodicalIF":5.9,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754818","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
Glial cell line derived neurotrophic factor (GDNF) induces mucosal healing via intestinal stem cell niche activation 胶质细胞系衍生神经营养因子(GDNF)通过肠道干细胞生态位激活诱导粘膜愈合。
IF 5.9 1区 生物学
Cell Proliferation Pub Date : 2024-11-28 DOI: 10.1111/cpr.13758
Marius Hörner, Natalie Burkard, Matthias Kelm, Antonia Leist, Thekla Selig, Catherine Kollmann, Michael Meir, Christoph Otto, Christoph-Thomas Germer, Kai Kretzschmar, Sven Flemming, Nicolas Schlegel
{"title":"Glial cell line derived neurotrophic factor (GDNF) induces mucosal healing via intestinal stem cell niche activation","authors":"Marius Hörner,&nbsp;Natalie Burkard,&nbsp;Matthias Kelm,&nbsp;Antonia Leist,&nbsp;Thekla Selig,&nbsp;Catherine Kollmann,&nbsp;Michael Meir,&nbsp;Christoph Otto,&nbsp;Christoph-Thomas Germer,&nbsp;Kai Kretzschmar,&nbsp;Sven Flemming,&nbsp;Nicolas Schlegel","doi":"10.1111/cpr.13758","DOIUrl":"10.1111/cpr.13758","url":null,"abstract":"<p>Mucosal healing is critical to maintain and restore intestinal homeostasis in inflammation. Previous data provide evidence that glial cell line-derived neurotrophic factor (GDNF) restores epithelial integrity by largely undefined mechanisms. Here, we assessed the role of GDNF for mucosal healing. In dextran sodium sulphate (DSS)-induced colitis in mice application of GDNF enhanced recovery as revealed by reduced disease activity index and histological inflammation scores. In biopsy-based wounding experiments GDNF application in mice improved healing of the intestinal mucosa. GDNF-induced epithelial recovery was also evident in wound assays from intestinal organoids and Caco2 cells. These observations were accompanied by an increased number of Ki67-positive cells in vivo after GDNF treatment, which were present along elongated proliferative areas within the crypts. In addition, the intestinal stem cell marker and R-spondin receptor LGR5 was significantly upregulated following GDNF treatment in all experimental models. The effects of GDNF on cell proliferation, LGR5 and Ki67 upregulation were blocked using the RET-specific inhibitor BLU-667. Downstream of RET-phosphorylation, activation of Src kinase was involved to mediate GDNF effects. GDNF promotes intestinal wound healing by promoting cell proliferation. This is mediated by RET-dependent activation of Src kinase with consecutive LGR5 upregulation, indicating activation of the stem cell niche.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"58 2","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13758","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749886","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}
引用次数: 0
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