The DPP8 Knockout HAP1 Polyclonal Cells product provides a CRISPR/Cas9-edited polyclonal knockout cell population targeting the human DPP8 gene in the HAP1 host background. This polyclonal knockout model introduces a loss-of-function disruption of DPP8, enabling robust investigation of its biological roles without the need for single-cell cloning. The engineered cell pool is designed to support targeted gene-knockout studies in a format that retains cellular heterogeneity, offering a versatile tool for researchers examining DPP8-dependent mechanisms in a human chronic myeloid leukemia-derived line.
HAP1 is a near-haploid human cell line originally derived from the KBM-7 chronic myeloid leukemia (CML) model. With a male, near-haploid karyotype, HAP1 cells contain only one copy of most chromosomes, simplifying genetic manipulation and loss-of-function analyses. This unique genomic architecture makes HAP1 a preferred platform for genetic screens, drug target validation, and signaling pathway dissection in a CML context. The cell line retains critical features of the parental leukemic cell, facilitating studies that bridge basic cellular mechanisms and hematological malignancy research.
Dipeptidyl peptidase 8 (DPP8) is a serine exopeptidase that cleaves N-terminal dipeptides from polypeptide substrates, regulating key processes such as immune cell activation and apoptosis. In the inflammasome signaling cascade, DPP8 inhibition or loss relieves a checkpoint on NLRP3 inflammasome assembly. Specifically, DPP8 disruption promotes NLRP3-dependent recruitment and activation of caspase-1, which proteolytically matures the pro-inflammatory cytokine IL-1?? and cleaves Gasdermin D to trigger pyroptotic cell death. Additionally, DPP8 interacts with its homologous protease DPP9 and modulates apoptotic pathways involving caspase-3/7. Upstream, DPP8 function is influenced by inflammatory cytokines including TNF-?? and IL-1??, placing it at a regulatory node connecting extracellular stimuli to inflammatory and cell-death responses.
In the HAP1 CML background, DPP8 knockout cells offer a genetically clean system to dissect DPP8-dependent signaling without compensatory expression from a second allele, due to the near-haploid constitution. This setting is particularly valuable for exploring how DPP8 loss influences leukemic cell survival, inflammasome-driven pyroptosis, and cross-talk between apoptosis and immune signaling. The model enables precise interrogation of DPP8’s role in the context of myeloid malignancy, aiding identification of vulnerabilities that may be exploited for therapeutic intervention in CML and other cancers characterized by dysregulated cell death pathways.
Key applications include inflammasome research, pyroptosis mechanism studies, drug target validation for DPP8 inhibitors, and cancer biology investigations. The knockout cells are compatible with a broad array of downstream assays such as western blotting for DPP8, caspase-1, and IL-1??; caspase-1 activity measurements; IL-1?? ELISA; LDH release assays for pyroptosis quantification; flow cytometry for cell death analysis; and co-immunoprecipitation for DPP8 interaction studies. For additional details and technical support, please contact Ascent Research.
