The DNER Knockout Raji Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the Raji human Burkitt lymphoma B lymphocyte cell line. This product facilitates targeted disruption of the DNER gene across a heterogeneous pool, enabling robust loss-of-function studies without the constraints of clonal selection. As a polyclonal knockout model, it retains population variability, making it suitable for investigating DNER-dependent phenotypes in a context that mirrors cellular diversity.
The Raji cell line was established from an EBV-positive Burkitt lymphoma and is a well-characterized model for B-cell biology and lymphomagenesis. These lymphoblastoid cells retain B-cell features including immunoglobulin production and involvement in adaptive immunity. The EBV-positive background introduces viral influences that can modify host cell signaling, providing a physiologically relevant platform to study how DNER disruption intersects with both normal and oncogenic B-cell pathways.
DNER functions as a type I transmembrane ligand for Notch receptors, selectively engaging NOTCH1, NOTCH2, and NOTCH3. Ligand?Creceptor interaction triggers a proteolytic cascade beginning with ADAM10/ADAM17 cleavage and subsequent ??-secretase-mediated release of the Notch intracellular domain (NICD). NICD translocates to the nucleus where it partners with CSL (RBPJ) and the coactivator MAML to activate transcription of downstream effectors including HES1, HES5, HEY1, HEY2, MYC, and CCND1. This signaling axis integrates upstream inputs from cytokines and developmental transcription factors that regulate DNER expression. By ablating DNER, the knockout model uncouples ligand-dependent Notch activation, allowing precise dissection of pathway dependencies.
In Raji B cells, Notch signaling modulates cell fate decisions, proliferation, and survival. DNER loss in this lymphoma-derived context permits examination of how ligand deficiency alters Notch target gene expression and downstream functional outcomes. Because deregulated Notch signaling is implicated in B- and T-cell malignancies, including acute lymphoblastic leukemia, this model is valuable for exploring DNER??s contribution to oncogenic processes. The interplay between DNER, EBV latency products, and B-cell differentiation pathways can be systematically investigated, potentially revealing novel therapeutic vulnerabilities.
Representative applications encompass Notch signaling characterization using co-culture assays, differentiation studies, and functional screens for Notch inhibitors. Researchers can measure protein and mRNA changes via Western blotting and RT-qPCR, monitor NICD nuclear occupancy by ChIP-qPCR, and assess target gene activation with Notch reporter assays. The polyclonal nature supports RNA-seq and flow cytometry-based analyses of population heterogeneity. Drug screening, apoptosis, and proliferation assays further extend the utility of these cells in cancer biology and immunology research. For further information, please contact Ascent Research.
