National Repository of Grey Literature 2 records found  Search took 0.01 seconds. 
Tcf4 transcription factor in the intestinal epithelium renewal and pathology
Müllerová, Tereza ; Janečková, Lucie (advisor) ; Vávra, Jiří (referee)
TCF4 (T-Cell Factor 4, sometimes also TCF7L2) is an important effector of the canonical Wnt signalling pathway. The transcription factor is produced in many different isoforms with tissue-specific expressionand diametricallyopposing functions.In the intestine,TCF4 is a key factor in epithelial regenerationandmaintenance of stem cell homeostasis. Its depletion causes loss of the proliferatingcrypt compartment and complete breakdown of the intestinal mucosal architecture. The processes in which it acts are therefore vital and must be strongly regulated by the Wnt signalling pathway. Disturbances in TCF4 expression or alternative splicing often lead to a wide range of complex pathologies such as colon cancer, ileal Crohn's disease and type 2 diabetes mellitus.
The role of TCF4 transcription factor in intestinal epithelial stem cells and tumors
Hrčkulák, Dušan ; Kořínek, Vladimír (advisor) ; Machoň, Ondřej (referee) ; Macůrková, Marie (referee)
For more than 20 years, T-cell specific factor 4 (Tcf4) is the most intensively studied member of the conserved Tcf/Lymphoid enhancer-binding factor (Lef) family of transcription factors. Together with β-catenin coactivator, Tcf4 represents the prominent nuclear effector of canonical Wnt signaling in the intestinal epithelium. Regulation of Wnt-β-catenin signaling in intestinal stem cells is crucial for tissue homeostasis and tumor formation initiation. Up to date, several mouse models were generated to manipulate Tcf4 abundance or activity in vivo and dissect its function. Moreover, mutational screens and expression profiling of human colorectal tumors were carried out to disclose a contribution of TCF4 to tumor progression. However, subsequent studies brought conflicting results in relation to the potential of Tcf4 to activate or repress Wnt target genes and drive or inhibit cell proliferation. Here in this study, we analyze publicly available datasets for global expression of TCF4 and its paralogs in human tissues and colorectal cancer (CRC) samples. Notably, we present newly generated Tcf4flox5 mouse with a conditional Tcf4 allele that can be used to eliminate expression of Tcf4 from two alternative promoters of the gene. Using this mouse strain we documented that Tcf4 loss led to the demise of...