The ACSS2 Knockout A-549 Polyclonal Cells product provides a CRISPR/Cas9-edited polyclonal knockout cell population derived from the A-549 human lung adenocarcinoma cell line, in which the ACSS2 gene has been disrupted to create a loss-of-function model. This polyclonal population is generated by CRISPR/Cas9-mediated gene targeting, resulting in a heterogeneous mixture of edited cells with ACSS2 ablation, enabling robust investigation of acetate metabolism without clonal variation biases.
The A-549 cell line originates from a human alveolar basal epithelial adenocarcinoma and serves as a widely used in vitro model for studying lung adenocarcinoma biology. These adherent epithelial cells recapitulate key features of non-small cell lung cancer, including oncogenic signaling pathways and metabolic adaptations characteristic of the disease. A-549 cells are commonly employed in proliferation assays, drug sensitivity studies, and metabolic analyses, making them a suitable host for interrogating cancer cell vulnerabilities.
ACSS2 encodes an acetyl-CoA synthetase that converts acetate to acetyl-CoA, a pivotal metabolite linking nutrient availability to lipid synthesis and histone acetylation. The product acetyl-CoA serves as a direct substrate for de novo lipogenesis via acetyl-CoA carboxylase (ACC) and fatty acid synthase (FASN) and as the acetyl donor for histone acetylation by p300/CBP, affecting marks such as H3K9ac and H3K27ac. Transcriptional regulation of ACSS2 is mediated by SREBP transcription factors and HIF-1??, integrating sterol and oxygen signals, while AMPK-dependent phosphorylation modulates enzymatic activity in response to energy status. Operating in concert with ACLY, ACC, FASN, and HMGCR, ACSS2 critically influences the acetyl-CoA pool that supports anabolic and epigenetic processes.
In the context of lung adenocarcinoma, ACSS2 is frequently upregulated and has been shown to support tumor cell proliferation and survival by maintaining acetyl-CoA pools necessary for membrane synthesis and histone acetylation-driven gene expression. The ACSS2 Knockout A-549 Polyclonal Cells enable researchers to directly assess the dependence of lung cancer cells on acetate metabolism and to explore how loss of this pathway alters lipid accumulation, epigenetic landscapes, and sensitivity to therapeutic agents. This model is therefore valuable for dissecting metabolic redundancy and identifying compensatory mechanisms that may limit anti-metabolic therapies.
This polyclonal knockout cell product is suited for functional assays including Western blotting to confirm ACSS2 loss and assess histone acetylation marks (H3K9ac, H3K27ac), RT-qPCR profiling of lipogenic genes, Seahorse metabolic flux analyses, and Oil Red O staining to visualize lipid droplets. Proliferation (MTT) and colony formation assays can gauge growth dependency, while drug sensitivity screens with cisplatin, etoposide, or metabolic inhibitors can uncover synthetic lethal interactions. The heterogeneous population also facilitates RNA-seq transcriptomic and ChIP-qPCR epigenomic studies. For further information, contact Ascent Research.
