This product is a CRISPR/Cas9-edited polyclonal knockout cell population in which the DLX4 gene has been disrupted in the HAP1 human cell line. The polyclonal composition encompasses a broad spectrum of gene disruption events, ensuring effective ablation of DLX4 function across the population. This population-based model is suitable for bulk assays and pooled screens.
The HAP1 cell line is a near-haploid human cell line derived from the KBM-7 chronic myeloid leukemia (CML) blast crisis line. It retains a stable haploid karyotype for most chromosomes, except for a disomic region on chromosome 8, facilitating unambiguous genotype-phenotype correlations. HAP1 is extensively employed for genome-wide CRISPR screens and as a disease model for myeloid leukemia research.
DLX4 is a homeobox transcription factor with essential roles in embryonic development, notably in limb and craniofacial morphogenesis, and is aberrantly expressed in multiple cancers. It operates downstream of BMP4 and FGF8, and its activity is influenced by retinoic acid and WNT3A. DLX4 directly regulates genes central to epithelial-mesenchymal transition, such as CDH1 (E-cadherin) and VIM (vimentin), as well as MMP2 and HOXB7, thereby controlling cell adhesion, migration, and invasion. It forms transcriptional complexes with MSX1, SMAD4, and LEF1, integrating signals from BMP, Wnt/??-catenin, and Notch pathways. Representative signaling mediators include WNT3A, Frizzled receptors, ??-catenin, BMP4, BMPR1A, and SMAD1, positioning DLX4 as a key transcriptional effector.
In the HAP1 near-haploid myeloid background, DLX4 disruption provides a powerful system to investigate its role in hematologic malignancies, particularly acute myeloid leukemia, where DLX4 may contribute to oncogenic transformation and drug resistance. The haploid genotype simplifies the analysis of loss-of-function phenotypes, such as changes in cell proliferation, differentiation, or apoptosis, without interference from a second allele. This model is exceptionally suited for synthetic lethal screens to uncover therapeutic targets that selectively kill DLX4-deficient leukemia cells. Moreover, the polyclonal knockout pool introduces genetic heterogeneity that serves as an internal control, minimizing the risk of off-target artifacts in phenotypic studies.
This product supports diverse research applications: functional genomics to dissect DLX4-dependent gene networks, investigation of EMT mechanisms using western blotting (CDH1, VIM), transwell migration assays, and immunofluorescence, and drug target validation in melanoma by profiling compound sensitivity in the knockout background. The cells are also compatible with haploid genetic screens, RNA-seq, ChIP-qPCR, and routine cell-based assays such as proliferation and RT-qPCR. For additional details, please contact Ascent Research.
