AACS Knockout Jurkat Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population generated from the Jurkat T lymphoblastoid cell line. This model provides loss-of-function disruption of the AACS gene, which encodes acetoacetyl-CoA synthetase, an enzyme catalyzing the ligation of acetoacetate with CoA to form acetoacetyl-CoA. The polyclonal format avoids clonal selection artifacts while enabling robust gene disruption across the cell population, making it suitable for studying ketone body utilization and downstream lipid metabolism.
Jurkat cells were originally derived from the peripheral blood of a patient with acute T-cell leukemia and serve as a well-established model for T-cell signaling, leukemia biology, and metabolic studies. Their rapid proliferation and high metabolic activity render them particularly valuable for investigating metabolic reprogramming in cancer, while their genetic tractability facilitates knockout studies of genes involved in lipid and energy metabolism.
AACS functions at a critical metabolic junction, converting ketone bodies into lipogenic substrates. Acetoacetyl-CoA, produced by AACS, can be channeled into the mevalonate pathway via HMGCS1 to generate cholesterol through HMGCR, or converted to acetyl-CoA equivalents for fatty acid synthesis by FASN. Transcription of AACS is controlled by SREBP-1c, PPAR??, and LXR?? in response to insulin and glucose availability, thereby linking nutritional cues to lipid anabolism. Key interacting partners include coenzyme A, ATP, and ACAT, with downstream targets encompassing mevalonate, cholesterol, and fatty acids.
Disruption of AACS in Jurkat cells impairs the utilization of exogenous acetoacetate for lipid and cholesterol biosynthesis, directly impacting mevalonate pathway flux and membrane biogenesis. This knockout model is significant for studying the metabolic dependencies of leukemic T cells, as T-ALL cells often rely on alternative nutrient sources to sustain proliferation. By uncoupling ketone body catabolism from anabolic fates, the model permits dissection of metabolic checkpoints that could be exploited therapeutically in leukemia and metabolic syndrome.
Typical applications include acetoacetate consumption, lipid synthesis measurement, mevalonate pathway flux analysis, proliferation assays, and drug sensitivity testing. These cells support flow cytometry, Western blotting, and RT-qPCR for validation, facilitating studies in metabolic reprogramming, obesity, and T-cell metabolism. For further information, please contact Ascent Research.
