ACSS2 Knockout 143B Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human 143B osteosarcoma cell line. This loss-of-function model disrupts the ACSS2 gene, providing a tool to study acetate metabolism and acetyl-CoA-dependent processes. The polyclonal nature captures a spectrum of genetic edits, enabling population-level analysis without clonal selection bias.
The 143B cell line is a KRAS-transformed human osteosarcoma model with high tumorigenic and metastatic capacity in vivo. Originating from HOS cells, it is widely used to investigate osteosarcoma biology and bone metastasis. The aggressive phenotype demands elevated biosynthetic activity, making it an ideal host for examining metabolic vulnerabilities, particularly those involving acetate utilization.
ACSS2 encodes cytosolic acetyl-CoA synthetase, catalyzing acetate-to-acetyl-CoA conversion essential for lipid synthesis and histone acetylation. Under metabolic stress, such as nutrient deprivation or hypoxia, ACSS2 is upregulated by SREBP1 and HIF-1??. The generated acetyl-CoA fuels fatty acid synthesis via FASN and ACC, and histone H3K27 acetylation by p300/CBP, promoting c-Myc target gene expression. ACSS2 interacts with AMPK and importins, integrating with ACLY at a key metabolic branch point. Knockout of ACSS2 thus deprives cells of a critical acetyl-CoA source, impairing anabolic and epigenetic programs.
In 143B osteosarcoma cells, ACSS2 knockout uncovers dependencies on acetate for sustaining proliferation and metastasis. Osteosarcomas often rely on exogenous acetate when glucose-derived acetyl-CoA is insufficient. Disrupting ACSS2-mediated acetyl-CoA production compromises lipid biosynthesis and histone acetylation, reducing tumor cell fitness under nutrient-limited conditions. This model therefore helps elucidate how KRAS-driven signaling intersects with acetate metabolism to support bone tumorigenesis.
Researchers can apply this polyclonal knockout product for acetate metabolism studies using acetyl-CoA quantification and fatty acid synthesis assays. Epigenetic profiling via ChIP-qPCR for H3K27ac and transcriptomic analysis by RNA-seq reveal downstream regulatory changes. Functional assays including MTT, Transwell migration, and drug sensitivity testing allow phenotypic assessment of metabolic inhibitors. These cells are suitable for screening anti-cancer agents targeting acetate utilization pathways. For further information, please contact Ascent Research.
