The JAK1 Knockout HAP1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population designed for loss-of-function analysis of the human JAK1 gene. This product consists of a heterogeneous pool of HAP1 cells carrying targeted gene disruptions introduced via CRISPR/Cas9 technology, enabling population-level studies of JAK1-dependent signaling pathways without the need for single-cell cloning.
The parental HAP1 cell line is a near-haploid human line derived from KBM-7, a chronic myeloid leukemia cell line isolated from a patient in blast crisis. Due to its haploid karyotype, HAP1 provides an ideal platform for genetic perturbation, as a single allelic modification results in a functional knockout, simplifying the interpretation of genotype-phenotype relationships in signaling research.
JAK1 encodes a non-receptor tyrosine kinase that serves as a critical mediator of cytokine receptor signaling. It is activated downstream of receptors including IFNAR, IL-6R, and IL-2R, and in turn phosphorylates STAT transcription factors such as STAT1, STAT3, STAT5, and STAT6. Phosphorylated STATs dimerize, translocate to the nucleus, and regulate gene expression programs driving immune responses, cell proliferation, and differentiation. JAK1 functions in concert with other JAK family kinases (JAK2, JAK3, TYK2) and is regulated by adaptors (IRS1, GRB2) and negative feedback components, notably SOCS3 and SHP2.
In the HAP1 background, JAK1 knockout provides an unambiguous loss-of-function model, as the haploid genome eliminates the possibility of residual wild-type alleles. This is particularly advantageous for studying JAK-STAT signaling in a hematopoietic context, given HAP1’s origin from a CML blast crisis patient. The model enables precise dissection of JAK1’s role in cytokine responses and can be used to explore how JAK-STAT dysregulation contributes to leukemogenesis and immune disorders. The polyclonal nature ensures the cells retain population diversity, making them suitable for assays requiring large, consistent cell numbers.
Researchers can employ these JAK1 knockout HAP1 cells in diverse applications, including cytokine stimulation assays with downstream analysis of phospho-STAT by western blotting, RT-qPCR quantification of STAT target genes, and flow cytometric assessment of cell-surface markers. The cells are also well-suited for high-throughput screening of JAK inhibitors, reporter assays for STAT transcriptional activity, and proliferation studies to evaluate cytokine-dependence. For additional technical specifications or ordering information, please contact Ascent Research.