This product consists of a CRISPR/Cas9-edited polyclonal knockout cell population derived from the KYSE-30 cell line, in which the ACSS2 gene has been disrupted to generate a heterogeneous pool of loss-of-function cells. The polyclonal format provides a mixed population carrying diverse editing events, avoiding clonal artifacts and enabling robust assessment of ACSS2-dependent phenotypes without the selective pressure of single-cell cloning. This model is optimized for researchers investigating acetate metabolism and its roles in cancer cell biology.
KYSE-30 is a well-differentiated human esophageal squamous cell carcinoma (ESCC) cell line originally isolated from a 64-year-old male patient. It is widely utilized as an in vitro model for ESCC, retaining key oncogenic and metabolic features of the primary tumor. Its robust growth in standard culture conditions and well-characterized signaling landscape make it a valuable system for dissecting tumor-specific dependencies, particularly those related to nutrient utilization and epigenetic control.
Acyl-CoA synthetase short-chain family member 2 (ACSS2) is the primary enzyme responsible for converting acetate into acetyl-CoA, a critical metabolic intermediate that feeds into both de novo lipogenesis and histone acetylation. Under metabolic stress conditions such as hypoxia or nutrient limitation, ACSS2 is transcriptionally upregulated by SREBP1, SREBP2, and HIF-1??, and its activity is modulated through AMPK- and SIRT1-mediated interactions. The acetyl-CoA produced by ACSS2 directly supports fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC) for lipid synthesis, and serves as a substrate for histone acetyltransferases including p300/CBP, thereby promoting H3K27 acetylation and permissive chromatin states at pro-survival and lipogenic gene loci.
In the KYSE-30 ESCC context, ACSS2-mediated acetate assimilation is considered a key contributor to the metabolic flexibility that sustains tumor cell proliferation and survival under nutrient-limited microenvironments. The knockout of ACSS2 in this polyclonal model disrupts both lipid biosynthesis and the epigenetic landscape, potentially impairing tumorigenic properties such as colony formation and anabolic growth. This provides a physiologically relevant platform to interrogate the interplay between metabolism, chromatin regulation, and oncogenic signaling in esophageal squamous cell carcinoma.
This ACSS2 knockout model supports a wide range of targeted investigations, including stable-isotope 13C-acetate tracing to map carbon flux, seahorse metabolic flux analysis to evaluate glycolytic and oxidative parameters, lipid droplet staining to assess lipogenic output, ChIP-qPCR for quantifying H3K27ac enrichment at target promoters, and RNA-seq or RT-qPCR to profile transcriptional changes in downstream effectors such as FASN and ACC. It is also amenable to drug sensitivity screens aimed at identifying synthetic lethal interactions with inhibitors of lipid metabolism or epigenetic modifiers. For further information about this product or related custom models, please contact Ascent Research.
