title: Ell3 enhances differentiation of mouse embryonic stem cells by regulating epithelial-mesenchymal transition and apoptosis.
abstract: Ell3 is a testis-specific RNA polymerase II elongation factor whose cellular function is not clear. The present study shows that Ell3 is activated during the differentiation of mouse embryonic stem cells (mESCs). Furthermore, Ell3 plays a critical role in stimulating lineage differentiation of mESCs by promoting epithelial-mesenchymal transition (EMT) and suppressing apoptosis. Mouse ESCs engineered to stably express Ell3 were rapidly differentiated compared with control cells either under spontaneous differentiation or neural lineage-specific differentiation conditions. Gene expression profile and quantitative RT-PCR analysis showed that the expression of EMT markers, such as Zeb1 and Zeb2, two major genes that regulate EMT, was upregulated in Ell3-overexpressing mESCs. Remarkably, knockdown of Zeb1 attenuated the enhanced differentiation capacity of Ell3-overexpressing mESCs, which indicates that Ell3 plays a role in the induction of mESC differentiation by inducing EMT. In contrast to Ell3-overexpressing mESCs, Ell3-knock down mESCs could not differentiate under differentiation conditions and, instead, underwent caspase-dependent apoptosis. In addition, apoptosis of differentiating Ell3-knock out mESCs was associated with enhanced expression of p53. The present results suggest that Ell3 promotes the differentiation of mESCs by activating the expression of EMT-related genes and by suppressing p53 expression.
authors: Department of Biomedical Science, College of Life Science, CHA University, Seoul, Korea.
authors: Hee-Jin
authors: HJ
authors: Ahn
authors: Young
authors: Y
authors: Cha
authors: Seok-Ho
authors: SH
authors: Moon
authors: Jee-Eun
authors: JE
authors: Jung
authors: Kyung-Soon
authors: KS
authors: Park
mesh_terms: D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction; D035602:Transcriptional Elongation Factors / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: C576409:Ell3 protein, mouse; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; D035602:Transcriptional Elongation Factors; D016159:Tumor Suppressor Protein p53; C519422:ZEB1 protein, mouse; D000071799:Zinc Finger E-box-Binding Homeobox 1; D020169:Caspases