The DYNC2H1 Knockout K-562 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the K-562 human immortalized myelogenous leukemia cell line, featuring targeted disruption of the DYNC2H1 gene. This loss-of-function model is generated using CRISPR/Cas9-mediated gene disruption, providing a heterogeneous pool of edited cells for studying DYNC2H1 functions in a hematopoietic context. The polyclonal format avoids clonal selection biases, enabling robust assessment of gene disruption effects across a diverse cell population.
The host K-562 cell line was established from the pleural effusion of a 53-year-old female with chronic myeloid leukemia in blast crisis and is Philadelphia chromosome positive, expressing the BCR-ABL1 fusion oncogene. This well-characterized suspension cell line serves as a widely used model for hematopoietic differentiation, leukemia biology, and drug response studies. Its rapid proliferation and ease of genetic manipulation make it an ideal platform for functional genomics, including CRISPR knockout screens and targeted gene ablation in blood lineage cells.
DYNC2H1 encodes the heavy chain subunit of the cytoplasmic dynein-2 motor complex, which is essential for retrograde intraflagellar transport (IFT) within cilia. The dynein-2 complex, containing interacting partners such as DYNC2LI1, DYNC2I1, WDR34, and WDR60, powers the movement of IFT particles toward the ciliary base, enabling recycling of signaling components. This process is critical for ciliogenesis and proper Hedgehog pathway signaling, where the GLI family of transcription factors (GLI1, GLI2, GLI3) mediate transcriptional responses. Upstream regulators like RFX transcription factors and FOXJ1 control DYNC2H1 expression, while its activity ensures proper processing of Hedgehog receptors PTCH1 and SMO, as well as downstream effectors such as SUFU, to regulate target genes including PTCH1, HHIP, and CCND1.
Although K-562 cells are traditionally considered non-ciliated, emerging evidence suggests that ciliary genes can have non-ciliary functions relevant to cancer cell biology. Introduction of DYNC2H1 knockout into this leukemic background permits exploration of potential moonlighting roles in processes such as proliferation, apoptosis, and chemoresistance, independent of cilia. This model bridges ciliopathy-associated gene function with hematological malignancy studies, offering a unique tool to dissect DYNC2H1 contributions beyond skeletal dysplasias and ciliopathies.
This polyclonal DYNC2H1 knockout cell population supports a broad range of experimental applications, including validation of CRISPR editing via Sanger sequencing, Western blotting, and RT-qPCR. Functional assays such as proliferation assays, apoptosis assays, and drug sensitivity profiling can delineate the gene’s impact on leukemia cell behavior. High-throughput approaches like RNA-seq enable transcriptome-wide analysis of DYNC2H1 loss, while targeted study of Hedgehog pathway components (e.g., GLI1, GLI2) under DYNC2H1 deficiency can reveal crosstalk with aberrant BCR-ABL1 signaling. For additional information or custom inquiries, please contact Ascent Research.
