The ALDH1A1 Knockout 786-O Polyclonal Cells consist of a CRISPR/Cas9-mediated gene-disrupted polyclonal cell population targeting the ALDH1A1 locus in the human 786-O renal cell carcinoma line. This polyclonal knockout model provides a heterogeneous pool of loss-of-function variants, enabling functional studies of ALDH1A1 without clonal selection bias. The product is derived from 786-O cells and supplied as a ready-to-use polyclonal population, facilitating experiments in cancer cell biology and retinoid signaling.
The 786-O cell line originates from a primary clear cell adenocarcinoma of the kidney and is characterized by biallelic inactivation of the von Hippel?CLindau (VHL) tumor suppressor gene. This VHL deficiency leads to constitutive stabilization of hypoxia-inducible factors (HIFs), driving a pseudohypoxic transcriptional program that promotes angiogenesis, glycolytic metabolism, and tumor progression. As a well-established model of clear cell renal cell carcinoma (ccRCC), 786-O cells are widely employed to investigate oncogenic signaling, metabolic rewiring, and therapeutic resistance mechanisms in kidney cancer.
ALDH1A1 encodes a cytosolic aldehyde dehydrogenase that catalyzes the oxidation of retinaldehyde to retinoic acid, a potent morphogen involved in gene regulation. Retinoic acid binds to heterodimeric retinoic acid receptors (RAR??/RXR??) and cellular retinoic acid-binding proteins (CRABP), thereby orchestrating transcription of target genes such as HOX clusters and CYP26A1. ALDH1A1 expression is regulated by upstream signaling pathways including Wnt/??-catenin, NF-??B, Notch, FOXM1, and PPAR??, while its enzymatic activity is dependent on NAD+ cofactor availability. Downstream, retinoic acid signaling modulates effectors like p21, influencing cell differentiation and proliferation. Disruption of ALDH1A1 abolishes the principal enzymatic source of retinoic acid in these cells, resulting in impaired RAR/RXR-mediated transcriptional control.
In the context of VHL-deficient 786-O cells, loss of ALDH1A1 disrupts retinoic acid biosynthesis, which may impact cancer stem cell maintenance and the differentiation state. Given that ALDH1 activity is a functional marker of cancer stem cells in renal carcinoma, its knockout provides a valuable tool to study stemness and self-renewal mechanisms. Additionally, retinoic acid signaling cross-talks with hypoxia-driven pathways, and ALDH1A1 knockout can reveal its role in chemoresistance and metabolic adaptation. This model allows researchers to dissect how ALDH1A1 contributes to renal tumor biology beyond its canonical detoxification function.
This polyclonal knockout cell population is suited for a range of experimental applications, including cancer stem cell biology assays, retinoic acid signaling studies, and drug resistance investigations. Representative assays include ALDEFLUOR flow cytometry to measure ALDH activity, RT-qPCR or Western blotting for ALDH1A1 and downstream targets, sphere formation assays to assess stem cell potential, and cytotoxicity assays to evaluate chemosensitivity. The cells can also be used for retinoic acid quantification via LC-MS or reporter assays. For further details and ordering information, please contact Ascent Research.
