Cell Proliferation最新文献_第10页

Optimizing in vitro T cell differentiation by using induced pluripotent stem cells with GFP-RUNX1 and mCherry-TCF7 labelling 利用带有 GFP-RUNX1 和 mCherry-TCF7 标记的诱导多能干细胞优化体外 T 细胞分化。

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2024-06-10 DOI: 10.1111/cpr.13661

Yu Zhao, Jiani Cao, Haoyu Xu, Weiyun Cao, Chenxi Cheng, Shaojing Tan, Tongbiao Zhao

{"title":"Optimizing in vitro T cell differentiation by using induced pluripotent stem cells with GFP-RUNX1 and mCherry-TCF7 labelling","authors":"Yu Zhao, Jiani Cao, Haoyu Xu, Weiyun Cao, Chenxi Cheng, Shaojing Tan, Tongbiao Zhao","doi":"10.1111/cpr.13661","DOIUrl":"10.1111/cpr.13661","url":null,"abstract":"In vitro T-cell differentiation from pluripotent stem cells (PSCs) could potentially provide an unlimited source of T cells for cancer immunotherapy, which, however is still hindered by the inefficient obtaining functionally-matured, terminally-differentiated T cells. Here, we established a fluorescence reporter human induced pluripotent stem cell (iPSC) line termed TCF7mCherryRUNX1GFP, in which the endogenous expression of RUNX1 and TCF7 are illustrated by the GFP and mCherry fluorescence, respectively. Utilizing TCF7mCherryRUNX1GFP, we defined that the feeder cells incorporating CXCL12-expressing OP9 cells with DL4-expressing OP9 cells at a 1:3 ratio (OP9-C1D3) significantly enhanced efficiency of CD8+ T cell differentiation from PSCs. Additionally, we engineered a chimeric antigen receptor (CAR) targeting EGFR into iPSCs. The CAR-T cells differentiated from these iPSCs using OP9-C1D3 feeders demonstrated effective cytotoxicity toward lung cancer cells. We anticipate this platform will help the in vitro HSPC and T cell differentiation optimization, serving the clinical demands of these cells.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"57 10","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13661","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295617","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

DCAF2 regulates the proliferation and differentiation of mouse progenitor spermatogonia by targeting p21 and thymine DNA glycosylase DCAF2 通过靶向 p21 和胸腺嘧啶 DNA 糖基化酶调节小鼠精原细胞的增殖和分化

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2024-06-04 DOI: 10.1111/cpr.13676

Hongwei Wei, Zhijuan Wang, Yating Huang, Longwei Gao, Weiyong Wang, Shuang Liu, Yan-Li Sun, Huiyu Liu, Yashuang Weng, Heng-Yu Fan, Meijia Zhang

{"title":"DCAF2 regulates the proliferation and differentiation of mouse progenitor spermatogonia by targeting p21 and thymine DNA glycosylase","authors":"Hongwei Wei, Zhijuan Wang, Yating Huang, Longwei Gao, Weiyong Wang, Shuang Liu, Yan-Li Sun, Huiyu Liu, Yashuang Weng, Heng-Yu Fan, Meijia Zhang","doi":"10.1111/cpr.13676","DOIUrl":"10.1111/cpr.13676","url":null,"abstract":"DDB1-Cullin-4-associated factor-2 (DCAF2, also known as DTL or CDT2), a conserved substrate recognition protein of Cullin-RING E3 ligase 4 (CRL4), recognizes and degrades several substrate proteins during the S phase to maintain cell cycle progression and genome stability. Dcaf2 mainly expressed in germ cells of human and mouse. Our study found that Dcaf2 was expressed in mouse spermatogonia and spermatocyte. The depletion of Dcaf2 in germ cells by crossing Dcaf2fl/fl mice with stimulated by retinoic acid gene 8(Stra8)-Cre mice caused a reduction in progenitor spermatogonia and differentiating spermatogonia, eventually leading to the failure of meiosis initiation and male infertility. Further studies showed that depletion of Dcaf2 in germ cells caused abnormal accumulation of the substrate proteins, cyclin-dependent kinase inhibitor 1A (p21) and thymine DNA glycosylase (TDG), decreasing of cell proliferation, increasing of DNA damage and apoptosis. Overexpression of p21 or TDG attenuates proliferation and increases DNA damage and apoptosis in GC-1 cells, which is exacerbated by co-overexpression of p21 and TDG. The findings indicate that DCAF2 maintains the proliferation and differentiation of progenitor spermatogonia by targeting the substrate proteins p21 and TDG during the S phase.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"57 10","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13676","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141257732","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

Comparison of seven CD19 CAR designs in engineering NK cells for enhancing anti-tumour activity 比较七种 CD19 CAR 设计在设计 NK 细胞以增强抗肿瘤活性方面的作用。

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2024-06-03 DOI: 10.1111/cpr.13683

Yao Wang, Jianhuan Li, Zhiqian Wang, Yanhong Liu, Tongjie Wang, Mengyun Zhang, Chengxiang Xia, Fan Zhang, Dehao Huang, Leqiang Zhang, Yaoqin Zhao, Lijuan Liu, Yanping Zhu, Hanmeng Qi, Xiaofan Zhu, Wenbin Qian, Fangxiao Hu, Jinyong Wang

{"title":"Comparison of seven CD19 CAR designs in engineering NK cells for enhancing anti-tumour activity","authors":"Yao Wang, Jianhuan Li, Zhiqian Wang, Yanhong Liu, Tongjie Wang, Mengyun Zhang, Chengxiang Xia, Fan Zhang, Dehao Huang, Leqiang Zhang, Yaoqin Zhao, Lijuan Liu, Yanping Zhu, Hanmeng Qi, Xiaofan Zhu, Wenbin Qian, Fangxiao Hu, Jinyong Wang","doi":"10.1111/cpr.13683","DOIUrl":"10.1111/cpr.13683","url":null,"abstract":"Chimeric antigen receptor-natural killer (CAR-NK) cell therapy is emerging as a promising cancer treatment, with notable safety and source diversity benefits over CAR-T cells. This study focused on optimizing CAR constructs for NK cells to maximize their therapeutic potential. We designed seven CD19 CAR constructs and expressed them in NK cells using a retroviral system, assessing their tumour-killing efficacy and persistence. Results showed all constructs enhanced tumour-killing and prolonged survival in tumour-bearing mice. In particular, CAR1 (CD8 TMD-CD3ζ SD)-NK cells showed superior efficacy in treating tumour-bearing animals and exhibited enhanced persistence when combined with OX40 co-stimulatory domain. Of note, CAR1-NK cells were most effective at lower effector-to-target ratios, while CAR4 (CD8 TMD-OX40 CD- FcεRIγ SD) compromised NK cell expansion ability. Superior survival rates were noted in mice treated with CAR1-, CAR2 (CD8 TMD- FcεRIγ SD)-, CAR3 (CD8 TMD-OX40 CD- CD3ζ SD)- and CAR4-NK cells over those treated with CAR5 (CD28 TMD- FcεRIγ SD)-, CAR6 (CD8 TMD-4-1BB CD-CD3ζ 1-ITAM SD)- and CAR7 (CD8 TMD-OX40 CD-CD3ζ 1-ITAM SD)-NK cells, with CAR5-NK cells showing the weakest anti-tumour activity. Increased expression of exhaustion markers, especially in CAR7-NK cells, suggests that combining CAR-NK cells with immune checkpoint inhibitors might improve anti-tumour outcomes. These findings provide crucial insights for developing CAR-NK cell products for clinical applications.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"57 11","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13683","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141236855","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

MicroRNA-3061 downregulates the expression of PAX7/Wnt/Ca2+ signalling axis genes to induce premature ovarian failure in mice MicroRNA-3061 下调 PAX7/Wnt/Ca2+ 信号轴基因的表达，诱导小鼠卵巢早衰。

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2024-06-03 DOI: 10.1111/cpr.13686

Te Liu, Yichao Wen, Zeyu Cui, Haiyang Chen, Jiajia Lin, Jianghong Xu, Danping Chen, Ying Zhu, Zhihua Yu, Chunxia Wang, Bimeng Zhang

{"title":"MicroRNA-3061 downregulates the expression of PAX7/Wnt/Ca2+ signalling axis genes to induce premature ovarian failure in mice","authors":"Te Liu, Yichao Wen, Zeyu Cui, Haiyang Chen, Jiajia Lin, Jianghong Xu, Danping Chen, Ying Zhu, Zhihua Yu, Chunxia Wang, Bimeng Zhang","doi":"10.1111/cpr.13686","DOIUrl":"10.1111/cpr.13686","url":null,"abstract":"The in-depth mechanisms of microRNA regulation of premature ovarian failure (POF) remain unclear. Crispr-cas9 technology was used to construct transgenic mice. The qPCR and Western blot was used to detect the expression level of genes. H&E staining were used to detect ovarian pathological phenotypes. We found that the expression levels of microRNA-3061 were significantly higher in ovarian granulosa cells (OGCs) of POF mouse models than in controls. The miR-3061+/−/AMH-Cre+/− transgenic mice manifested symptoms of POF. RNA-Seq and luciferase reporter assay confirmed that the PAX7 was one of the target genes negatively regulated by microRNA-3061 (miR-3061–5p). Moreover, PAX7 mediated the expression of non-canonical Wnt/Ca2+ signalling pathway by binding to the motifs of promoters to stimulate the transcriptional activation of Wnt5a and CamK2a. In contrast, specific knock-in of microRNA-3061 in OGCs significantly downregulated the expression levels of PAX7 and inhibited the expression of downstream Wnt/Ca2+ signalling pathway. We also discerned a correlation between the expression levels of mRNAs of the Wnt/Ca2+ signalling pathway and the levels of E2 and FSH in POF patients by examining gene expression in the follicular fluid-derived exosomes of women. We confirmed that overexpression of microRNA-3061 induced proliferative inhibition of OGCs and ultimately induced POF in mice by suppressing the transcription factor PAX7 and downregulating expression levels of its downstream Wnt/Ca2+ signalling pathway genes.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"57 11","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13686","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141236857","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

AAV-mediated gene therapy restores natural fertility and improves physical function in the Lhcgr-deficient mouse model of Leydig cell failure AAV介导的基因疗法可恢复Lhcgr缺陷小鼠的自然生育能力并改善其生理功能。

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2024-05-30 DOI: 10.1111/cpr.13680

Suyuan Zhang, Bin Yang, Xiaoting Shen, Hong Chen, Fulin Wang, Zhipeng Tan, Wangsheng Ou, Cuifeng Yang, Congyuan Liu, Hao Peng, Peng Luo, Limei Peng, Zhenmin Lei, Sunxing Yan, Tao Wang, Qiong Ke, Chunhua Deng, Andy Peng Xiang, Kai Xia

{"title":"AAV-mediated gene therapy restores natural fertility and improves physical function in the Lhcgr-deficient mouse model of Leydig cell failure","authors":"Suyuan Zhang, Bin Yang, Xiaoting Shen, Hong Chen, Fulin Wang, Zhipeng Tan, Wangsheng Ou, Cuifeng Yang, Congyuan Liu, Hao Peng, Peng Luo, Limei Peng, Zhenmin Lei, Sunxing Yan, Tao Wang, Qiong Ke, Chunhua Deng, Andy Peng Xiang, Kai Xia","doi":"10.1111/cpr.13680","DOIUrl":"10.1111/cpr.13680","url":null,"abstract":"Leydig cell failure (LCF) caused by gene mutations leads to testosterone deficiency, infertility and reduced physical function. Adeno-associated virus serotype 8 (AAV8)-mediated gene therapy shows potential in treating LCF in the Lhcgr-deficient (Lhcgr−/−) mouse model. However, the gene-treated mice still cannot naturally sire offspring, indicating the modestly restored testosterone and spermatogenesis in AAV8-treated mice remain insufficient to support natural fertility. Recognizing this, we propose that enhancing gene delivery could yield superior results. Here, we screened a panel of AAV serotypes through in vivo transduction of mouse testes and identified AAVDJ as an impressively potent vector for testicular cells. Intratesticular injection of AAVDJ achieved markedly efficient transduction of Leydig cell progenitors, marking a considerable advance over conventional AAV8 vectors. AAVDJ-Lhcgr gene therapy was well tolerated and resulted in significant recovery of testosterone production, substantial improvement in sexual development, and remarkable restoration of spermatogenesis in Lhcgr−/− mice. Notably, this therapy restored fertility in Lhcgr−/− mice through natural mating, enabling the birth of second-generation. Additionally, this treatment led to remarkable improvements in adipose, muscle, and bone function in Lhcgr−/− mice. Collectively, our findings underscore AAVDJ-mediated gene therapy as a promising strategy for LCF and suggest its broader potential in addressing various reproductive disorders.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"57 9","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13680","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178961","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

Tetrahedral framework nucleic acid–based small-molecule inhibitor delivery for ecological prevention of biofilm 基于四面体框架核酸的小分子抑制剂递送，用于生物膜生态预防。

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2024-05-29 DOI: 10.1111/cpr.13678

Yuhao Liu, Kechen Li, Weijie Zhuang, Lulu Liang, Xiangyi Chen, Dongsheng Yu

{"title":"Tetrahedral framework nucleic acid–based small-molecule inhibitor delivery for ecological prevention of biofilm","authors":"Yuhao Liu, Kechen Li, Weijie Zhuang, Lulu Liang, Xiangyi Chen, Dongsheng Yu","doi":"10.1111/cpr.13678","DOIUrl":"10.1111/cpr.13678","url":null,"abstract":"Biofilm formation constitutes the primary cause of various chronic infections, such as wound infections, gastrointestinal inflammation and dental caries. While preliminary achievement of biofilm inhibition is possible, the challenge lies in the difficulty of eliminating the bactericidal effects of current drugs that lead to microbiota imbalance. This study, utilizing in vitro and in vivo models of dental caries, aims to efficiently inhibit biofilm formation without inducing bactericidal effects, even against pathogenic bacteria. The tetrahedral framework nucleic acid (tFNA) was employed as a delivery vector for a small-molecule inhibitor (smI) specifically targeting the activity of glucosyltransferases C (GtfC). It was observed that tFNA loaded smI in a small-groove binding manner, efficiently transferring it into Streptococcus mutans, thereby inhibiting GtfC activity and extracellular polymeric substances formation without compromising bacterial survival. Furthermore, smI-loaded tFNA demonstrated a reduction in the severity of dental caries in vivo without adversely affecting oral microbial diversity and exhibited desirable topical and systemic biosafety. This study emphasizes the concept of ‘ecological prevention of biofilm’, which is anticipated to advance the optimization of biofilm prevention strategies and the clinical application of DNA nanocarrier-based drug formulations.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"57 9","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13678","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141173723","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

RETRACTION: miR-664a-3p functions as an oncogene by targeting Hippo pathway in the development of gastric cancer 返回：miR-664a-3p 在胃癌的发展过程中通过靶向 Hippo 通路发挥致癌基因的功能。

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2024-05-28 DOI: 10.1111/cpr.13681

引用次数: 0

RETRACTION: Six2 Promotes Non–Small Cell Lung Cancer Cell Stemness Via Transcriptionally and Epigenetically Regulating E-Cadherin 返回：Six2 通过转录和表观遗传调控 E-Cadherin，促进非小细胞肺癌细胞的干性。

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2024-05-28 DOI: 10.1111/cpr.13682

引用次数: 0

Pyroptotic macrophages induce disruption of glutamate metabolism in periodontal ligament stem cells contributing to their compromised osteogenic potential 嗜火巨噬细胞会扰乱牙周韧带干细胞的谷氨酸代谢，导致其成骨细胞潜能受损。

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2024-05-27 DOI: 10.1111/cpr.13663

Li-Juan Sun, Hong-Lei Qu, Xiao-Tao He, Bei-Min Tian, Rui-Xin Wu, Yuan Yin, Jie-Kang Zou, Hai-Hua Sun, Xuan Li, Fa-Ming Chen

{"title":"Pyroptotic macrophages induce disruption of glutamate metabolism in periodontal ligament stem cells contributing to their compromised osteogenic potential","authors":"Li-Juan Sun, Hong-Lei Qu, Xiao-Tao He, Bei-Min Tian, Rui-Xin Wu, Yuan Yin, Jie-Kang Zou, Hai-Hua Sun, Xuan Li, Fa-Ming Chen","doi":"10.1111/cpr.13663","DOIUrl":"10.1111/cpr.13663","url":null,"abstract":"Macrophage pyroptosis is of key importance to host defence against pathogen infections and may participate in the progression and recovery of periodontitis. However, the role of pyroptotic macrophages in regulating periodontal ligament stem cells (PDLSCs), the main cell source for periodontium renewal, remains unclear. First, we found that macrophage pyroptosis were enriched in gingiva tissues from periodontitis patients compared with those of healthy people through immunofluorescence. Then the effects of pyroptotic macrophages on the PDLSC osteogenic differentiation were investigated in a conditioned medium (CM)-based coculture system in vitro. CM derived from pyroptotic macrophages inhibited the osteogenic differentiation-related gene and protein levels, ALP activity and mineralized nodule formation of PDLSCs. The osteogenic inhibition of CM was alleviated when pyroptosis was inhibited by VX765. Further, untargeted metabolomics showed that glutamate limitation may be the underlying mechanism. However, exogenous glutamate supplementation aggravated the CM-inhibited osteogenic differentiation of PDLSCs. Moreover, CM increased extracellular glutamate and decreased intracellular glutamate levels of PDLSCs, and enhanced the gene and protein expression levels of system xc− (a cystine/glutamate antiporter). After adding cystine to CM-based incubation, the compromised osteogenic potency of PDLSCs was rescued. Our data suggest that macrophage pyroptosis is related to the inflammatory lesions of periodontitis. Either pharmacological inhibition of macrophage pyroptosis or nutritional supplements to PDLSCs, can rescue the compromised osteogenic potency caused by pyroptotic macrophages.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"57 10","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13663","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157991","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

Tissue specific stem cell therapy for airway regeneration 用于气道再生的组织特异性干细胞疗法。

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2024-05-27 DOI: 10.1111/cpr.13662

Dan Bi Park, Jae Yoon Lee, Sung Won Kim, Do Hyun Kim

引用次数: 0