The IL6ST Knockout HAP1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population that features targeted disruption of the IL6ST gene in the human near-haploid HAP1 cell line. This polyclonal knockout model provides a genetically heterogeneous pool of cells lacking functional gp130 expression, enabling loss-of-function studies without single-cell clonal isolation. The product is designed to support robust interrogation of IL6ST-dependent signaling pathways in a well-characterized genetic background.
The HAP1 host cell line is derived from a chronic myeloid leukemia patient and retains a near-haploid karyotype, which simplifies genetic manipulation and facilitates clear genotype-phenotype correlations in functional genomics research. HAP1 cells are widely used as a model system for knockout screens, drug target validation, and mechanistic signaling studies due to their stable haploid state and ease of culture. Their adherent growth and human origin make them particularly suitable for studying cytokine signaling pathways relevant to human disease.
The IL6ST gene encodes gp130, the common signal-transducing receptor subunit shared by the interleukin-6 (IL-6) family of cytokines, including IL-6, LIF, OSM, CNTF, IL-11, IL-27, CTF1, and CLCF1. Upon ligand binding to the corresponding alpha receptor, gp130 homodimerizes or heterodimerizes with LIFR or OSMR, leading to activation of associated Janus kinases (JAK1, JAK2, TYK2) and subsequent phosphorylation of downstream transcription factors STAT3, STAT1, and STAT5. Additionally, gp130 signaling engages the MAPK cascade and PI3K-Akt pathway through the recruitment of SHP2 and GRB2. Key targets include SOCS3, a negative feedback regulator, as well as BCL2L1, MMP9, VEGF, CRP, and SAA, which mediate cell survival, migration, and acute-phase responses.
In the HAP1 background, disruption of IL6ST abrogates gp130-dependent signaling, providing a clean loss-of-function model to dissect the contributions of JAK/STAT, MAPK, and PI3K pathways to cellular phenotypes. The near-haploid nature of HAP1 cells ensures that a single gene copy is targeted, increasing the likelihood of complete protein loss across the polyclonal population and reducing genetic redundancy. This model is particularly valuable for studying gp130-mediated oncogenic signaling in malignancies such as multiple myeloma and hepatocellular carcinoma, as well as in inflammatory disorders like rheumatoid arthritis and Castleman disease.
The IL6ST Knockout HAP1 Polyclonal Cells are suitable for a wide range of research applications, including cytokine stimulation assays with phospho-STAT3 detection by western blotting or flow cytometry, RT-qPCR analysis of IL6-responsive genes, and RNA-seq transcriptome profiling to map gp130-dependent transcriptional networks. Functional studies can include cell proliferation and apoptosis assays, as well as JAK inhibitor sensitivity testing to validate therapeutic targets. These cells also serve as a powerful tool for functional genomics screens and drug target validation for gp130 inhibitors. For additional information or technical support, please contact Ascent Research.
