The HDHD2 Knouckout SK-HEP-1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal population with disrupted HDHD2 gene in the SK-HEP-1 human hepatic endothelial cell line. This loss-of-function model provides a genetically heterogeneous pool for studying HDHD2 ablation consequences. The polyclonal format circumvents clonal variation, and the product targets researchers investigating nucleotide metabolism and pseudouridine biology.
SK-HEP-1 is an ascites-derived adenocarcinoma cell line with endothelial-like features, used as a liver sinusoidal endothelial and hepatocellular carcinoma model. Exhibiting both epithelial and endothelial characteristics, it is valuable for hepatic pathophysiology, angiogenesis, and tumor microenvironment studies. The HDHD2 knockout in this background leverages its liver biology relevance for nucleotide metabolism research.
The HDHD2 gene encodes a pseudouridine-5′-phosphatase that catalyzes the dephosphorylation of pseudouridine 5′-phosphate to pseudouridine, a critical step in pyrimidine metabolism and the nucleotide salvage pathway. This enzymatic activity regulates intracellular pseudouridine levels and contributes to nucleotide pool homeostasis. Although upstream regulatory mechanisms and interacting proteins remain to be identified, HDHD2 functions as a key enzymatic node linking modified nucleoside catabolism to broader metabolic networks. Disruption of HDHD2 is expected to perturb pseudouridine metabolism and may affect nucleotide-dependent cellular processes, though the precise phenotypic outcomes are context-dependent and warrant systematic investigation.
Within the SK-HEP-1 background, the HDHD2 knockout model provides a physiologically relevant system for examining the crosstalk between pseudouridine salvage and liver cell function. Given the liver’s prominent role in nucleotide recycling and the dual endothelial?Cepithelial nature of SK-HEP-1 cells, this knockout enables exploration of how perturbations in pyrimidine metabolism influence hepatocellular carcinoma phenotypes and sinusoidal endothelial biology. Since the biological functions of HDHD2 remain underexplored, this model offers a unique opportunity to discover novel metabolic liabilities in liver cancer, potentially linking pseudouridine metabolism to tumor progression or drug response.
This polyclonal knockout product is suitable for diverse experimental workflows, including knockout confirmation via western blotting and RT-qPCR, quantification of pseudouridine and related nucleotides by LC-MS, cell proliferation assays, and metabolic flux analyses using stable isotope-labeled precursors to trace pyrimidine pathway activity. The polyclonal format allows researchers to capture a range of editing events and study heterogeneous population-level effects, making it apt for functional genomics screens and stress-response experiments. For technical inquiries or ordering, please contact Ascent Research.
