Direct in vivo conversion of astrocytes into functional new neurons induced by neural transcription factors has been recognized as a potential new therapeutic intervention for neural injury and degenerative disorders....Direct in vivo conversion of astrocytes into functional new neurons induced by neural transcription factors has been recognized as a potential new therapeutic intervention for neural injury and degenerative disorders. However, a few recent studies have claimed that neural transcription factors cannot convert astrocytes into neurons, attributing the converted neurons to pre-existing neurons mis-expressing transgenes. In this study, we overexpressed three distinct neural transcription factors––NeuroD1, Ascl1, and Dlx2––in reactive astrocytes in mouse cortices subjected to stab injury, resulting in a series of significant changes in astrocyte properties. Initially, the three neural transcription factors were exclusively expressed in the nuclei of astrocytes. Over time, however, these astrocytes gradually adopted neuronal morphology, and the neural transcription factors was gradually observed in the nuclei of neuron-like cells instead of astrocytes. Furthermore,we noted that transcription factor-infected astrocytes showed a progressive decrease in the expression of astrocytic markers AQP4(astrocyte endfeet signal), CX43(gap junction signal), and S100β. Importantly, none of these changes could be attributed to transgene leakage into preexisting neurons. Therefore, our findings suggest that neural transcription factors such as NeuroD1, Ascl1, and Dlx2 can effectively convert reactive astrocytes into neurons in the adult mammalian brain.展开更多
Objective:To elucidate the role and clinical potential of the lncRNA DLX6-AS1/miR-26a/PTEN axis in liver fibrosis.Methods:Systematic studies were conducted using cellular and animal models through causal validation,bi...Objective:To elucidate the role and clinical potential of the lncRNA DLX6-AS1/miR-26a/PTEN axis in liver fibrosis.Methods:Systematic studies were conducted using cellular and animal models through causal validation,bivariate experiments,single-cell sequencing,ROC analysis of clinical samples,and humanized mouse models.Results:LncRNA DLX6-AS1 inhibited PTEN by adsorbing miR-26a,promoting hepatic stellate cell activation in a dose/time-dependent manner;the axis demonstrated excellent diagnostic performance(AUC>0.9),and its inhibitors effectively reversed fibrosis in vivo.Conclusion:This study provides new biomarkers and targeted therapeutic strategies for liver fibrosis.展开更多
目的:探讨无远端同源异源盒3(Distal-Less Homeobox 3,DLX3)在结肠癌中的预后及其免疫学作用。方法:利用癌症基因组图谱(The Cancer Genome Atlas,TCGA)、基因表达合成(Gene Expression Omnibus,GEO)数据集、人蛋白图谱(Human Protein A...目的:探讨无远端同源异源盒3(Distal-Less Homeobox 3,DLX3)在结肠癌中的预后及其免疫学作用。方法:利用癌症基因组图谱(The Cancer Genome Atlas,TCGA)、基因表达合成(Gene Expression Omnibus,GEO)数据集、人蛋白图谱(Human Protein Atlas,HPA)和生物信息学工具,探讨DLX3在结肠癌中的表达及与患者预后、免疫细胞浸润和分子特征的关系。结果:结肠癌患者中存在大量突变的基因,与正常组织相比,DLX3在肿瘤组织中表达量上升,同时随着癌症分级增加,DLX3的表达量也随之上升。DLX3表达水平与B细胞、CD8^(+)T细胞、中性粒细胞、树突状细胞浸润水平呈负相关,与CD4+T细胞、巨噬细胞浸润水平呈正相关。DLX3与多种肿瘤浸润免疫细胞亚型相关,其中Th2、Act_CD4和Tem_CD8与DLX3相关性最强;DLX3与不同免疫亚型和分子亚型相关。结肠癌中DLX3不同体细胞拷贝数变化与肿瘤细胞免疫浸润相关。DLX3高表达组结肠癌患者的总生存时间明显缩短(p=0.0019)。结论:DLX3具备作为结肠癌病理诊断标志物的潜在价值,有望成为结肠癌患者预后判断的新型分子标记物,具有较高的临床价值。展开更多
目的基于骨组织Dlx5启动子甲基化水平,探索补肾中药复方对大鼠去卵巢骨质疏松症的疗效机制。方法去卵巢建立绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)大鼠模型,分为正常组、模型组、补肾中药复方组、仙灵骨葆阳性对照组。灌...目的基于骨组织Dlx5启动子甲基化水平,探索补肾中药复方对大鼠去卵巢骨质疏松症的疗效机制。方法去卵巢建立绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)大鼠模型,分为正常组、模型组、补肾中药复方组、仙灵骨葆阳性对照组。灌胃14周后,X线吸收测量法检测骨密度,质谱法检测Dlx5启动子甲基化水平。结果与正常组比较,模型组第1~6腰椎骨密度明显降低(P<0.01),骨组织Dlx5启动子-470 bp^-4 bp CpG2.3甲基化水平明显升高(P<0.01)。②与模型组比较,补肾中药复方组、仙灵骨葆阳性对照组第1~6腰椎骨密度明显升高(P<0.05),骨组织Dlx5启动子-470 bp^-4 bp CpG1甲基化水平明显降低(P<0.05)。结论补肾中药复方通过降低骨组织Dlx5启动子甲基化水平的表观遗传学机制,有效防治PMOP。展开更多
基金supported by the Key Project of Guangzhou City,No.202206060002Science and Technology Project of Guangdong Province,No.2018B030332001Guangdong Provincial Pearl River Project,No.2021ZT09Y552 (all to GC)。
文摘Direct in vivo conversion of astrocytes into functional new neurons induced by neural transcription factors has been recognized as a potential new therapeutic intervention for neural injury and degenerative disorders. However, a few recent studies have claimed that neural transcription factors cannot convert astrocytes into neurons, attributing the converted neurons to pre-existing neurons mis-expressing transgenes. In this study, we overexpressed three distinct neural transcription factors––NeuroD1, Ascl1, and Dlx2––in reactive astrocytes in mouse cortices subjected to stab injury, resulting in a series of significant changes in astrocyte properties. Initially, the three neural transcription factors were exclusively expressed in the nuclei of astrocytes. Over time, however, these astrocytes gradually adopted neuronal morphology, and the neural transcription factors was gradually observed in the nuclei of neuron-like cells instead of astrocytes. Furthermore,we noted that transcription factor-infected astrocytes showed a progressive decrease in the expression of astrocytic markers AQP4(astrocyte endfeet signal), CX43(gap junction signal), and S100β. Importantly, none of these changes could be attributed to transgene leakage into preexisting neurons. Therefore, our findings suggest that neural transcription factors such as NeuroD1, Ascl1, and Dlx2 can effectively convert reactive astrocytes into neurons in the adult mammalian brain.
基金Study on the Correlation between the Regulation of the miR-26a/PTEN Axis by lncRNA DLX6-AS1 and Post-Hepatitis Liver Fibrosis(Project No.:YKK22233)。
文摘Objective:To elucidate the role and clinical potential of the lncRNA DLX6-AS1/miR-26a/PTEN axis in liver fibrosis.Methods:Systematic studies were conducted using cellular and animal models through causal validation,bivariate experiments,single-cell sequencing,ROC analysis of clinical samples,and humanized mouse models.Results:LncRNA DLX6-AS1 inhibited PTEN by adsorbing miR-26a,promoting hepatic stellate cell activation in a dose/time-dependent manner;the axis demonstrated excellent diagnostic performance(AUC>0.9),and its inhibitors effectively reversed fibrosis in vivo.Conclusion:This study provides new biomarkers and targeted therapeutic strategies for liver fibrosis.
文摘目的:探讨无远端同源异源盒3(Distal-Less Homeobox 3,DLX3)在结肠癌中的预后及其免疫学作用。方法:利用癌症基因组图谱(The Cancer Genome Atlas,TCGA)、基因表达合成(Gene Expression Omnibus,GEO)数据集、人蛋白图谱(Human Protein Atlas,HPA)和生物信息学工具,探讨DLX3在结肠癌中的表达及与患者预后、免疫细胞浸润和分子特征的关系。结果:结肠癌患者中存在大量突变的基因,与正常组织相比,DLX3在肿瘤组织中表达量上升,同时随着癌症分级增加,DLX3的表达量也随之上升。DLX3表达水平与B细胞、CD8^(+)T细胞、中性粒细胞、树突状细胞浸润水平呈负相关,与CD4+T细胞、巨噬细胞浸润水平呈正相关。DLX3与多种肿瘤浸润免疫细胞亚型相关,其中Th2、Act_CD4和Tem_CD8与DLX3相关性最强;DLX3与不同免疫亚型和分子亚型相关。结肠癌中DLX3不同体细胞拷贝数变化与肿瘤细胞免疫浸润相关。DLX3高表达组结肠癌患者的总生存时间明显缩短(p=0.0019)。结论:DLX3具备作为结肠癌病理诊断标志物的潜在价值,有望成为结肠癌患者预后判断的新型分子标记物,具有较高的临床价值。
文摘目的基于骨组织Dlx5启动子甲基化水平,探索补肾中药复方对大鼠去卵巢骨质疏松症的疗效机制。方法去卵巢建立绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)大鼠模型,分为正常组、模型组、补肾中药复方组、仙灵骨葆阳性对照组。灌胃14周后,X线吸收测量法检测骨密度,质谱法检测Dlx5启动子甲基化水平。结果与正常组比较,模型组第1~6腰椎骨密度明显降低(P<0.01),骨组织Dlx5启动子-470 bp^-4 bp CpG2.3甲基化水平明显升高(P<0.01)。②与模型组比较,补肾中药复方组、仙灵骨葆阳性对照组第1~6腰椎骨密度明显升高(P<0.05),骨组织Dlx5启动子-470 bp^-4 bp CpG1甲基化水平明显降低(P<0.05)。结论补肾中药复方通过降低骨组织Dlx5启动子甲基化水平的表观遗传学机制,有效防治PMOP。
