The HLCS Knockout Jurkat Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population targeting the HLCS gene in Jurkat T lymphocytes. This product consists of a heterogeneous pool of edited cells with gene disruptions, avoiding clonal selection artifacts and providing a population-level loss-of-function model. The polyclonal format is well-suited for bulk biochemical and functional assays, ensuring robust representation of editing outcomes.
Jurkat cells are an immortalized T lymphocyte line derived from a patient with acute T cell leukemia. They are extensively used to study T cell receptor signaling, apoptosis, and cancer biology. Their rapid growth and well-defined signaling pathways make them a versatile host for knockout models. The T cell context is particularly valuable for examining immunometabolism and metabolic reprogramming in leukemia.
The HLCS gene encodes holocarboxylase synthetase, a key enzyme in biotin metabolism that catalyzes the covalent attachment of biotin to lysine residues of apocarboxylases. This post-translational modification activates biotin-dependent carboxylases, including propionyl-CoA carboxylase (PCC), pyruvate carboxylase (PC), 3-methylcrotonyl-CoA carboxylase (MCC), and acetyl-CoA carboxylase (ACC). HLCS is transcriptionally regulated by SP1 and activated by biotin availability. It also interacts with histones, hinting at broader cellular roles. Loss of HLCS function leads to multiple carboxylase deficiency, organic acid accumulation, and metabolic acidosis.
In Jurkat T cells, HLCS knockout disrupts biotin-dependent metabolic pathways critical for lymphocyte function. T cell activation requires dynamic metabolic reprogramming, including increased glycolysis and oxidative phosphorylation. By impairing carboxylase biotinylation, these polyclonal cells perturb TCA cycle anaplerosis, fatty acid synthesis, and amino acid catabolism. This model enables investigation of how metabolic dysregulation affects TCR signaling, apoptosis, and proliferation, making it a valuable resource for immunometabolism and leukemia research.
Typical applications include Western blot and biotinylation assays to monitor HLCS expression and substrate modification, together with carboxylase activity measurements and metabolic flux analysis using isotope labeling. When combined with T cell activation assays??such as CD3/CD28 stimulation and cytokine profiling??these cells help elucidate the role of biotin metabolism in immune responses. They also serve as a model for holocarboxylase synthetase deficiency and multiple carboxylase deficiency research. For additional information, please contact Ascent Research.
