Knockdown of human TCF4 affects multiple signaling pathways involved in cell survival, epithelial to mesenchymal transition and neuronal differentiation.
Knockdown of human TCF4 affects multiple signaling pathways involved in cell survival, epithelial to mesenchymal transition and neuronal differentiation.
复制标题
DOI：
10.1371/journal.pone.0073169
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Blake DJ
中科院分区：
文献类型：
--
作者：
Forrest MP;Waite AJ;Martin-Rendon E;Blake DJ
TCF4 的单倍体不足会导致皮特-霍普金斯综合征 (PTHS)：一种严重的精神发育迟滞，其表型与 Angelman、Mowat-Wilson 和 Rett 综合征相似。全基因组关联研究还发现，TCF4 的常见变异与精神分裂症风险增加相关。尽管 TCF4 是转录因子，但人们对大脑中 TCF4 调节过程知之甚少。在这项研究中，我们使用全基因组表达谱来确定急性 TCF4 敲低对 SH-SY5Y 神经母细胞瘤细胞基因表达的影响。我们在 TCF4 敲除细胞中发现了 1204 个基因表达变化（494 个上调，710 个下调）。对 TCF4 敲低细胞中差异表达基因的通路和富集分析发现，参与 TGF-β 信号传导、上皮间质转化 (EMT) 和细胞凋亡的基因过度表达。最显着差异表达的基因是 EMT 调节因子 SNAI2 和 DEC1 以及原神经基因 NEUROG2 和 ASCL1。在 TCF4 耗尽的细胞中还发现了几种智力低下基因的表达改变，例如 UBE3A（天使综合症）、ZEB2（莫瓦特-威尔逊综合症）和 MEF2C。这些数据表明，除了临床上重要的智力低下基因的子集外，TCF4 还调节许多涉及细胞分化和存活的汇聚信号通路。
Haploinsufficiency of TCF4 causes Pitt-Hopkins syndrome (PTHS): a severe form of mental retardation with phenotypic similarities to Angelman, Mowat-Wilson and Rett syndromes. Genome-wide association studies have also found that common variants in TCF4 are associated with an increased risk of schizophrenia. Although TCF4 is transcription factor, little is known about TCF4-regulated processes in the brain. In this study we used genome-wide expression profiling to determine the effects of acute TCF4 knockdown on gene expression in SH-SY5Y neuroblastoma cells. We identified 1204 gene expression changes (494 upregulated, 710 downregulated) in TCF4 knockdown cells. Pathway and enrichment analysis on the differentially expressed genes in TCF4-knockdown cells identified an over-representation of genes involved in TGF-β signaling, epithelial to mesenchymal transition (EMT) and apoptosis. Among the most significantly differentially expressed genes were the EMT regulators, SNAI2 and DEC1 and the proneural genes, NEUROG2 and ASCL1. Altered expression of several mental retardation genes such as UBE3A (Angelman Syndrome), ZEB2 (Mowat-Wilson Syndrome) and MEF2C was also found in TCF4-depleted cells. These data suggest that TCF4 regulates a number of convergent signaling pathways involved in cell differentiation and survival in addition to a subset of clinically important mental retardation genes.
登录
查看更多内容
影响因子：
10.6
作者：
Brzozka, Magdalena M.;Radyushkin, Konstantin;Rossner, Moritz J.
通讯作者：
Rossner, Moritz J.
影响因子：
4
作者：
Bolós, V;Peinado, H;Cano, A
通讯作者：
Cano, A
影响因子：
56.9
作者：
HENTHORN, P;KILEDJIAN, M;KADESCH, T
通讯作者：
KADESCH, T
骨形态发生蛋白在神经干细胞命运和成熟中的动态作用。
影响因子：
3
作者：
Bond, Allison M.;Bhalala, Oneil G.;Kessler, John A.
通讯作者：
Kessler, John A.
影响因子：
14.9
作者：
Edgar, R;Domrachev, M;Lash, AE
通讯作者：
Lash, AE