The HNF4A Knockout 769-P Polyclonal Cells product provides a CRISPR/Cas9-edited polyclonal 769-P cell population harboring targeted disruption of the HNF4A gene. This genetically heterogeneous knockout pool allows functional interrogation of HNF4A loss in a malignant renal epithelial context. HNF4A encodes a nuclear receptor transcription factor critical for hepatic and epithelial gene regulation, and its ablation is associated with metabolic reprogramming and dedifferentiation.
The parental 769-P line is a clear cell renal cell carcinoma model derived from proximal tubule epithelium. These cells retain hallmark features of renal adenocarcinoma, including tumorigenic capacity, and serve as a standard platform for studying renal cancer biology and epithelial-specific gene regulation.
HNF4A operates as a ligand-dependent transcription factor that recruits coactivators such as PPARGC1A (PGC-1??), CREBBP/p300, and NCOA1 to modulate target gene expression. Its activity is influenced by upstream energy sensors AMPK and SIRT1, and cooperates with pioneer factors HNF1?? and FoxA2 in epithelial gene networks. Downstream, HNF4A directly transactivates metabolic and structural genes: lipid transport (APOA1), serum proteins (ALB, TTR), bile acid synthesis (CYP7A1), glucose handling (SLC2A2/GLUT2, PKLR), and tight junction constituents OCLN and CDH1. Dynamic repression is achieved via corepressors NCOR1 and HDACs.
In 769-P clear cell renal carcinoma cells, HNF4A knockout dismantles epithelial integrity and metabolic organization. Loss of OCLN and CDH1 disrupts tight junctions and promotes EMT and invasive potential. Concurrent suppression of fatty acid oxidation (PPARA, CPT1A), glycolysis (GCK), and xenobiotic metabolism (CYP3A4) forces a metabolic shift characteristic of aggressive renal tumors. This polyclonal knockout system thus models the dual phenotypic and metabolic consequences of HNF4A deficiency in kidney cancer.
This polyclonal knockout population supports diverse investigational workflows: validation by western blot and RT-qPCR for HNF4A and targets (APOA1, OCLN); transcriptomic profiling via RNA-seq; ChIP-qPCR for HNF4A binding; immunofluorescence of OCLN/CDH1 to assess barrier function; migration and invasion assays; and metabolic flux analysis by Seahorse. Drug response and viability assays enable screening in an HNF4A-null background. These approaches facilitate studies on HNF4A??s role in renal carcinoma metabolism, EMT, and drug sensitivity. For further information, contact Ascent Research.
