DLL1 Knockout HAP1 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population designed to disrupt the DLL1 gene (Delta-like 1) in the near-haploid HAP1 human cell line. This knockout model provides a powerful loss-of-function tool for investigating the Notch signaling pathway and DLL1-dependent cellular processes. The use of a polyclonal population ensures diverse knockout variants while maintaining overall gene disruption, suitable for functional genetic analyses.
The HAP1 cell line is a near-haploid human cell line derived from the KBM-7 chronic myeloid leukemia (CML) line. Its near-haploid karyotype, with a single copy of most chromosomes, facilitates unambiguous gene disruption, as a single CRISPR/Cas9-mediated editing event can lead to functional gene knockout. This characteristic makes HAP1 an ideal host for genetic screens and mechanistic studies, particularly in signal transduction pathways relevant to leukemia and hematopoiesis.
DLL1 encodes a transmembrane ligand for Notch receptors (NOTCH1?C4). Upon binding to Notch on adjacent cells, DLL1 triggers sequential proteolytic cleavages by ADAM10 and the ??-secretase complex, releasing the Notch intracellular domain (NICD). NICD translocates to the nucleus, where it forms a transcriptional activation complex with CSL (RBPJ) and MAML, directly upregulating target genes such as HES1, HES5, HEY1, and HEY2. DLL1 activity is modulated by upstream regulators including MESP2, TBX6, and Wnt/FGF signaling, and its signaling converges on downstream effectors like MYC, CCND1, and NFKB1, influencing cell fate decisions, proliferation, and differentiation.
In the HAP1 background, DLL1 knockout disrupts Notch-mediated cell-cell communication, a pathway critically involved in hematopoiesis and leukemogenesis. The near-haploid nature of HAP1 cells ensures that DLL1 disruption results in a clean loss-of-function, avoiding confounding effects from heterozygous expression. This model is particularly relevant for studying the role of Notch signaling in myeloid leukemia, T-cell acute lymphoblastic leukemia (T-ALL), and developmental disorders such as Adams-Oliver syndrome and spondylocostal dysostosis. By abolishing DLL1 function, researchers can dissect kinase- and transcription factor-independent mechanisms in Notch-driven phenotypes.
This knockout cell population is suitable for a broad range of applications, including Notch reporter assays, Western blotting for DLL1 and downstream targets (e.g., HES1, HEY1), RT-qPCR profiling of Notch target genes, and flow cytometric analysis of Notch receptor surface expression. Co-culture signaling assays can be employed to evaluate intercellular Notch activation, while migration, invasion, and apoptosis assays allow investigation of DLL1-dependent malignant phenotypes. Additionally, the polyclonal format is ideal for pooled CRISPR screens and drug sensitivity studies targeting the Notch pathway. For further information, please contact Ascent Research.
