The DPP9 Knockout HAP1 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal cell population derived from the HAP1 human haploid leukemic cell line, designed for targeted disruption of the DPP9 gene. This heterogeneous pool of loss-of-function alleles provides a robust model for studying the biological consequences of DPP9 deficiency without relying on single-cell clonal expansion, thereby preserving functional diversity and reducing clonal artifacts. The polyclonal format is especially suited for pooled screening approaches and studies requiring representation of multiple editing outcomes across a population of cells.
The HAP1 host cell line is a near-haploid chronic myeloid leukemia (CML) line of male origin, exhibiting adherent morphology and a stable haploid karyotype. Its haploid nature simplifies genetic manipulation and facilitates unambiguous genotype-phenotype correlations, making it a preferred platform for functional genomics, drug target validation, and CRISPR-based screens. HAP1 retains key features of leukemic cells, including deregulated growth signaling, and serves as a relevant model for hematological cancer research.
DPP9 encodes a cytosolic serine protease belonging to the DPPIV family, which cleaves N-terminal dipeptides from polypeptide substrates and plays a critical role in regulating innate immune responses. The protease acts upstream of the NLRP1 and CARD8 inflammasomes by processing their N-termini, preventing spontaneous oligomerization and downstream signaling. DPP9 activity is modulated by inflammatory cytokines such as TNF-alpha and IFN-gamma, growth factors like EGF, and cellular stress conditions including hypoxia. Its key interacting partners include NLRP1, CARD8, and multiple putative substrate proteins. Loss of DPP9 function leads to constitutive assembly of NLRP1 and CARD8 inflammasomes, recruitment of ASC, and activation of caspase-1, which in turn promotes proteolytic maturation and secretion of IL-1?? and IL-18, ultimately triggering pyroptosis.
In the HAP1 leukemic background, DPP9 disruption offers a unique opportunity to dissect the crosstalk between inflammasome activation, pyroptosis, and leukemia biology. The haploid setting permits precise investigation of the DPP9-NLRP1/CARD8 axis without the confounding effects of gene compensation from additional alleles. This model enables researchers to explore how DPP9 loss influences cell survival, cytokine release, and cell death pathways in the context of leukemic signaling, and may inform on the role of inflammasome-driven inflammation in cancer progression and drug response.
These polyclonal knockout cells are suitable for a wide range of applications, including mechanistic studies of NLRP1 and CARD8 inflammasome regulation, screening for DPP9 substrates, and investigation of pyroptosis through assays such as western blotting, ELISA for IL-1??, ASC speck formation, and propidium iodide uptake. They also support functional analyses of cancer cell migration and viability, as well as testing of small-molecule modulators targeting the DPP9-inflammasome axis. The DPP9 Knockout HAP1 Polyclonal Cells thus provide a versatile and genetically tractable platform for immunology, oncology, and drug discovery research. For further assistance, please contact Ascent Research.
