论文库首页  论文库
 
论文编号:
论文题目: Aberrant transcriptional networks in step-wise neurogenesis of paroxysmal kinesigenic dyskinesia-induced pluripotent stem cells
英文论文题目: Aberrant transcriptional networks in step-wise neurogenesis of paroxysmal kinesigenic dyskinesia-induced pluripotent stem cells
第一作者: Li, C; Ma, Y; Zhang, KS; Gu, JJ; Tang, F; Chen, SD; Cao, L; Li, SG; Jin, Y
英文第一作者: Li, C; Ma, Y; Zhang, KS; Gu, JJ; Tang, F; Chen, SD; Cao, L; Li, SG; Jin, Y
联系作者: Jin, Y (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Ctr Excellence Mol & Cell Sci, Key Lab Stem Cell Biol,Inst Hlth Sci, Shanghai 200025, Peoples R China.
英文联系作者: Jin, Y (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Ctr Excellence Mol & Cell Sci, Key Lab Stem Cell Biol,Inst Hlth Sci, Shanghai 200025, Peoples R China.
外单位作者单位:
英文外单位作者单位:
发表年度: 2016
卷: 7
期: 33
页码: 53611-53627
摘要: Paroxysmal kinesigenic dyskinesia (PKD) is an episodic movement disorder with autosomal-dominant inheritance and marked variability in clinical manifestations. Proline-rich transmembrane protein 2 (PRRT2) has been identified as a causative gene of PKD, but the molecular mechanism underlying the pathogenesis of PKD still remains a mystery. The phenotypes and transcriptional patterns of the PKD disease need further clarification. Here, we report the generation and neural differentiation of iPSC lines from two familial PKD patients with c.487C>T (p. Gln163X) and c.573dupT (p. Gly192Trpfs*8) PRRT2 mutations, respectively. Notably, an extremely lower efficiency in neural conversion from PKD-iPSCs than control-iPSCs is observed by a step-wise neural differentiation method of dual inhibition of SMAD signaling. Moreover, we show the high expression level of PRRT2 throughout the human brain and the expression pattern of PRRT2 in other human tissues for the first time. To gain molecular insight into the development of the disease, we conduct global gene expression profiling of PKD cells at four different stages of neural induction and identify altered gene expression patterns, which peculiarly reflect dysregulated neural transcriptome signatures and a differentiation tendency to mesodermal development, in comparison to control-iPSCs. Additionally, functional and signaling pathway analyses indicate significantly different cell fate determination between PKD-iPSCs and control-iPSCs. Together, the establishment of PKD-specific in vitro models and the illustration of transcriptome features in PKD cells would certainly help us with better understanding of the defects in neural conversion as well as further investigations in the pathogenesis of the PKD disease.
英文摘要: Paroxysmal kinesigenic dyskinesia (PKD) is an episodic movement disorder with autosomal-dominant inheritance and marked variability in clinical manifestations. Proline-rich transmembrane protein 2 (PRRT2) has been identified as a causative gene of PKD, but the molecular mechanism underlying the pathogenesis of PKD still remains a mystery. The phenotypes and transcriptional patterns of the PKD disease need further clarification. Here, we report the generation and neural differentiation of iPSC lines from two familial PKD patients with c.487C>T (p. Gln163X) and c.573dupT (p. Gly192Trpfs*8) PRRT2 mutations, respectively. Notably, an extremely lower efficiency in neural conversion from PKD-iPSCs than control-iPSCs is observed by a step-wise neural differentiation method of dual inhibition of SMAD signaling. Moreover, we show the high expression level of PRRT2 throughout the human brain and the expression pattern of PRRT2 in other human tissues for the first time. To gain molecular insight into the development of the disease, we conduct global gene expression profiling of PKD cells at four different stages of neural induction and identify altered gene expression patterns, which peculiarly reflect dysregulated neural transcriptome signatures and a differentiation tendency to mesodermal development, in comparison to control-iPSCs. Additionally, functional and signaling pathway analyses indicate significantly different cell fate determination between PKD-iPSCs and control-iPSCs. Together, the establishment of PKD-specific in vitro models and the illustration of transcriptome features in PKD cells would certainly help us with better understanding of the defects in neural conversion as well as further investigations in the pathogenesis of the PKD disease.
刊物名称: ONCOTARGET
英文刊物名称: ONCOTARGET
论文全文:
英文论文全文:
全文链接:
其它备注:
英文其它备注:
学科: Oncology; Cell Biology
英文学科: Oncology; Cell Biology
影响因子: 5.168
第一作者所在部门:
英文第一作者所在部门:
论文出处:
英文论文出处:
论文类别: Article
英文论文类别: Article
参与作者:
英文参与作者:
 
2014 中国科学院上海生命科学研究院 版权所有