The IMPA2 Knockout HeLa Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population with disruption of the IMPA2 gene (inositol monophosphatase 2) in the HeLa human cervical adenocarcinoma cell line. This loss-of-function model is generated by CRISPR/Cas9-mediated gene disruption, yielding a heterogeneous pool of edited cells that preserves population-level diversity and avoids clonal selection artifacts, making it ideal for robust functional studies.
HeLa cells are an immortalized epithelial line derived from a cervical adenocarcinoma in 1951 and are positive for human papillomavirus type 18 (HPV18). As a widely characterized cancer cell model, HeLa provides a reproducible and well-defined background for investigating inositol phosphate metabolism and related signaling pathways, with extensive genomic, transcriptomic, and proteomic resources available to support knockout studies.
IMPA2 catalyzes the dephosphorylation of inositol monophosphate to myo-inositol, a critical step for phosphatidylinositol recycling that replenishes the phosphatidylinositol-4,5-bisphosphate (PIP2) pool. PIP2 serves as a substrate for phospholipase C (PLC) to generate IP3 and DAG, which mobilize calcium and activate PKC, while also supporting AKT signaling via PIP3. IMPA2 is inhibited by lithium and regulated by inositol homeostasis. Knockout of IMPA2 disrupts this recycling, attenuating PIP2-dependent cascades including AKT phosphorylation and PKC activation, and impairing calcium flux.
In HeLa cells, the IMPA2 knockout model disrupts phosphoinositide recycling and dampens signaling through growth factor receptors and GPCRs that converge on PIP2, providing a tool to study lithium’s mechanism of action. Lithium inhibits IMPA2 and is used in bipolar disorder and schizophrenia. This polyclonal cell population enables dissection of lithium-sensitive pathways and examination of how inositol depletion influences cancer cell proliferation, survival, and migration via AKT and PKC.
Key applications include investigating inositol metabolism and phosphatidylinositol signaling, lithium pharmacodynamics, and modeling neuropsychiatric disorders in a cell-based system. Compatible assays include Western blotting for IMPA2 and phospho-AKT, RT-qPCR validation, inositol monophosphate accumulation, calcium flux imaging, PIP2 quantification, lithium dose-response, and phospho-PKC flow cytometry; these cells also suit drug screening for IMPA inhibitors. For further information, please contact Ascent Research.
