The JAG2 Knockout 786-O Polyclonal Cells comprise a CRISPR/Cas9-edited polyclonal knockout cell population derived from the 786-O human clear cell renal cell carcinoma line, designed to ablate JAG2 gene function and eliminate Jagged-2 protein expression. This population is generated by CRISPR/Cas9-mediated gene disruption, offering a loss-of-function model that preserves the genetic heterogeneity of polyclonal knockout cells while enabling robust evaluation of Jagged-2-dependent signaling in a cancer-relevant context. The absence of Jagged-2 facilitates dissection of ligand-specific Notch pathway activation and its downstream cellular consequences.
The 786-O parental line is a well-characterized model of VHL-mutant clear cell renal cell carcinoma, derived from a primary renal tumor. Its constitutive HIF1A stabilization due to VHL loss creates a pseudohypoxic state that mimics key aspects of ccRCC biology, including altered angiogenesis and metabolism. The cells retain hallmark oncogenic features of ccRCC, making them a relevant system for studying tumorigenic mechanisms and therapeutic vulnerabilities. This genetic background is ideal for examining crosstalk between the VHL/HIF axis and developmental pathways such as Notch, where Jagged-2 ligands may integrate hypoxic and differentiation signals.
JAG2 encodes Jagged-2, a transmembrane ligand that activates NOTCH1?C4 receptors, initiating ??-secretase-mediated release of the Notch intracellular domain (NICD). NICD translocates to the nucleus, forming complexes with RBPJ and MAML co-activators to drive transcription of target genes including HES1, HEY1, MYC, and CCND1. JAG2 expression is regulated by hypoxia and HIF1A, and Notch signaling can further modulate its levels. Knockout of JAG2 in this polyclonal model eliminates Jagged-2, impairing ligand-dependent Notch activation and attenuating downstream transcriptional outputs. This disruption alters proliferation, differentiation, and survival signaling, providing a clean system to probe Jagged-2?CNotch interactions.
In VHL-mutant ccRCC cells, where HIF1A-driven programs intersect with Notch signaling, JAG2 knockout allows dissection of ligand-specific roles in tumor cell proliferation, migration, and epithelial-to-mesenchymal transition. The loss of Jagged-2 in 786-O cells may particularly impact Notch-mediated regulation of MYC and CCND1, which are implicated in renal cancer growth. Because JAG2 engages multiple Notch receptors, this model helps resolve receptor-specific contributions without endogenous Jagged-2 interference, clarifying how hypoxic environments modulate Notch-dependent oncogenic phenotypes.
This polyclonal JAG2 knockout product is suited for a wide range of experimental approaches to study Notch biology and renal carcinoma pathogenesis. Representative assays include Western blotting for JAG2 and Notch targets, RT-qPCR for HES/HEY family genes, flow cytometry with Notch activation reporters, proliferation and migration/invasion assays, RNA-seq transcriptomic profiling, and Notch reporter co-culture systems. It is also applicable to drug target validation, combining genetic loss of JAG2 with pharmacological inhibition of ??-secretase or NOTCH receptors. For further information, please contact Ascent Research.
