The HTT Knockout SK-HEP-1 Polyclonal Cells represent a polyclonal knockout cell population generated by CRISPR/Cas9-mediated disruption of the human HTT gene, eliminating functional huntingtin protein. This pool comprises a heterogeneous mix of targeted edits, providing a robust loss-of-function model that avoids clonal artifacts. It is well-suited for population-level studies, including pooled functional genomics screens and signaling analyses.
SK-HEP-1 is a human hepatic adenocarcinoma cell line, initially derived from ascitic fluid, that exhibits an endothelial-like phenotype with expression of von Willebrand factor and acetylated LDL uptake. These features make it a widely adopted model for hepatic sinusoidal endothelium, angiogenesis, and tumor cell plasticity in the liver microenvironment.
HTT encodes a large scaffolding protein pivotal for vesicular trafficking, endocytosis, cell adhesion, and autophagy. It interacts with HAP1, HIP1, HIP14, GAPDH, calmodulin, CBP, and p53, and is regulated by BDNF/TrkB signaling and caspase-6 cleavage. Downstream, HTT coordinates mTORC1, ULK1, Beclin-1, and DRP1, thereby controlling autophagy and mitochondrial dynamics. Loss of HTT function disrupts microtubule-based transport, impairs autophagic flux, and induces aberrant mitochondrial fission, leading to cellular stress and altered signaling cascades.
In the SK-HEP-1 hepatic endothelial-like adenocarcinoma model, HTT knockout enables dissection of huntingtin’s non-neuronal roles in liver pathophysiology. Given the cell line’s dual epithelial-endothelial nature, HTT loss may impact cell adhesion, migration, and angiogenic signaling, processes central to tumor progression. Furthermore, HTT’s involvement in endocytosis suggests that its disruption could modulate growth factor receptor trafficking and cytokine responses in the liver microenvironment, offering insights into autophagy?Ccancer interplay.
These polyclonal knockout cells support diverse applications, including mechanistic studies of Huntington’s disease in non-neuronal contexts, drug screening for HTT modulators, and functional mapping of the huntingtin interactome. Typical assays include western blotting, immunofluorescence, RT-qPCR, autophagy flux evaluation via LC3-II turnover, mitochondrial function assessment with MitoTracker, cell adhesion and transferrin uptake endocytosis assays, and viability testing. They also serve as a parental line for stable knockdown or rescue models. For detailed product information or technical support, please contact Ascent Research.
