The JAG2 Knockout 143B Polyclonal Cells are a CRISPR/Cas9-edited polyclonal population of 143B osteosarcoma cells with a targeted disruption of the JAG2 gene, encoding the Notch ligand Jagged-2. This polyclonal pool provides a heterogeneous loss-of-function model for studying JAG2-dependent signaling in a human mesenchymal tumor context.
The parental 143B cell line is a highly metastatic human osteosarcoma line derived from the HOS (human osteosarcoma) cell line. As a model of aggressive bone cancer with mesenchymal origin, 143B cells exhibit robust tumorigenic and metastatic properties, making them a widely used system for investigating osteosarcoma biology and cancer cell dissemination.
JAG2 functions as a canonical Notch ligand, acting upstream of NOTCH receptors (NOTCH1, NOTCH2, NOTCH3, NOTCH4). Upon cell-cell contact, JAG2 engagement triggers ADAM10/ADAM17-mediated S2 cleavage and subsequent ??-secretase (PSEN1) cleavage, releasing the Notch intracellular domain (NICD). NICD translocates to the nucleus, forming a transcriptional activation complex with CSL/RBPJ and MAML1 to induce expression of downstream targets such as HES1, HEY1, HEY2, MYC, and CCND1. JAG2 expression is transcriptionally regulated by NF-??B, HIF-1??, TGF-??, and Wnt/??-catenin signaling, integrating multiple inputs to control cell fate, proliferation, and apoptosis.
In the 143B osteosarcoma background, JAG2 knockout provides a powerful tool to dissect Notch-mediated mechanisms in tumor progression. Given the importance of Notch signaling in osteosarcoma metastasis and the role of JAG2 in promoting invasive phenotypes, this polyclonal population allows investigation of both cell-autonomous and non-autonomous effects within a mixed knockout context. Loss of JAG2 may disrupt Notch-dependent transcriptional programs, impacting proliferation, migration, and differentiation, and can be used to explore crosstalk with Wnt/??-catenin and NF-??B pathways frequently activated in osteosarcoma.
This knockout model is suited for a range of experimental approaches, including western blotting and RT-qPCR to monitor changes in JAG2 and its downstream targets (e.g., HES1, HEY1), Notch reporter assays to quantify signaling activity, and functional assays such as migration, invasion, and proliferation. Co-immunoprecipitation with NOTCH1 and RNA-seq analysis can further elucidate altered interactomes and transcriptomic signatures. It enables drug target validation for Notch pathway inhibitors and serves as a platform for studying developmental biology and oncogenic signaling. For additional details or to place an order, please contact Ascent Research.
