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基因谱系示踪技术揭示小鼠Tbx18^+心脏祖细胞向心系细胞分化的潜能 被引量:12
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作者 杜建霖 张进 +6 位作者 蒲荻 高二志 杨景涛 高凌志 夏爽 邓松柏 佘强 《生物化学与生物物理进展》 SCIE CAS CSCD 北大核心 2011年第2期127-133,共7页
心脏祖细胞(cardiac progenitor cells,CPCs)的研究对阐明先天性心脏病的机制及治疗心血管疾病具有重要意义.哺乳动物的心脏组织由多种不同CPCs分化形成.转录因子Tbx18在发育中的心外膜中表达,对心脏的发育形成起重要的调节作用.为了在... 心脏祖细胞(cardiac progenitor cells,CPCs)的研究对阐明先天性心脏病的机制及治疗心血管疾病具有重要意义.哺乳动物的心脏组织由多种不同CPCs分化形成.转录因子Tbx18在发育中的心外膜中表达,对心脏的发育形成起重要的调节作用.为了在组织及活体细胞水平检测和阐明Tbx18+CPC的分化潜能,应用Cre-LoxP系统建立Tbx18+CPCs基因命运谱系示踪模型:Tbx18-Cre/Rosa26R-EYFP和Tbx18-Cre/Rosa26R-LacZ双杂合基因敲入小鼠.该双杂合基因敲入小鼠通过Cre的表达能有效地示踪Tbx18+细胞在胚胎和成年小鼠中的分化命运.Tbx18-Cre/Rosa26R-EYFP双杂合小鼠心脏能非常容易地利用流式细胞分选系统(FACS)分离出YFP+细胞,也可在倒置共聚焦显微镜下观察.应用X-gal染色分析其表达模式,揭示Tbx18命运谱系参与心房肌、室间隔、心室肌、冠状动脉、瓣膜等的形成.应用免疫荧光技术初步揭示Tbx18+CPCs向心脏肌钙蛋白T(cTNT)阳性心肌细胞和平滑肌肌球蛋白重链11(MYH11)阳性血管平滑肌细胞分化的潜能.心脏是一个由多种肌肉和非肌肉组织细胞构成的复杂器官.推测Tbx18可能在心脏祖细胞向肌源性细胞分化的信号通路中起重要调节作用.在上述研究中应用基因谱系示踪技术,验证Tbx18可作为一类CPCs的标志,为更深入揭示心脏祖细胞向心系细胞的分化潜能打下基础. 展开更多
关键词 T—box转录因子18 心脏祖细胞 谱系示踪 心肌细胞
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Predicting tbx22 Zebrafish Protein Structure Using Multi-Level Prediction Tools and Demonstration of Conserved Structural Domains in Relation to Orthologous tbx22 Proteins in Humans
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作者 Vijay P. Boominathan Tracie Ferreira 《Journal of Biosciences and Medicines》 2016年第3期79-92,共14页
Biological functions of proteins play a key role in the development of any organism. The gene tbx 22 is a member of a phylogenetically conserved family of genes, which share a common DNA binding domain: T box. This st... Biological functions of proteins play a key role in the development of any organism. The gene tbx 22 is a member of a phylogenetically conserved family of genes, which share a common DNA binding domain: T box. This study examines the similarity in the developmental pattern influenced by the transcription factor TBX22 and tbx22 in H. sapiens and D. rerio respectively. Secondary and tertiary structures of the proteins are predicted using standard structure prediction software’s like Phyre 2, Predict Protein, SWISSMODEL, PSIPRED and the homology of the proteins were compared to each other. Protein homology prediction shows more than 65% between the 2 organisms. Superimposing the predicted protein structures reveals conserved domains between the human and zebrafish proteins. Additional supporting data from Genomatix MATBASE, MATINSPECTOR show higher matrix family scores for BRAC (Brachury gene mesoderm developmental factor) in Human and Zebrafish. Transcription factor and promoter element analysis with Transcriptome Viewer, Gene 2 Promoter and Genomeinspector reveal a high degree of homology between the 2 organisms. Bioinformatic-Proteomics and protein structural analysis approaches shown here explain in detail the relationship between the Human and Zebrafish tbx22 Gene-Protein-Transcrip- tion factor. These studies also support zebrafish as a predictive model for numerous developmental pattering events in higher vertebrates. 展开更多
关键词 t-box tbx22 transcription factors Genomatix Protein Prediction Superimposed Models
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