The JAGN1 Knockout HeLa Polyclonal Cells are a CRISPR/Cas9-edited polyclonal population of HeLa cells carrying targeted disruptions in the JAGN1 gene. This heterogeneous pool lacks clonal selection, providing a loss-of-function model that captures diverse editing outcomes. These cells are designed to eliminate JAGN1 protein expression, enabling studies of its role in endoplasmic reticulum (ER) homeostasis, secretory regulation, and downstream signaling pathways. The polyclonal format is ideal for experiments prioritizing population-level phenotypic analyses over single-clone behavior.
The HeLa host cell line originates from a HPV18-positive cervical adenocarcinoma, representing an epithelial cell type with robust secretory machinery. These cells are widely used in cancer biology, signal transduction, and drug discovery due to their rapid proliferation and ease of manipulation. Although HeLa cells are not of hematopoietic origin, their active ER and secretory pathways provide a relevant background for dissecting JAGN1 function. The epithelial context allows researchers to assess generalizable ER stress mechanisms independent of neutrophil-specific phenotypes, while still enabling comparative studies with neutrophil lineage models.
JAGN1 encodes an ER-resident protein that acts as a critical regulator of the unfolded protein response (UPR) and protein secretion. It physically interacts with the chaperone HSPA5 (BiP) and other UPR modulators including HSP90B1 and HYOU1. Upstream, JAGN1 responds to ER stress inducers and is linked to activation of UPR sensors ERN1 (IRE1), ATF6, and EIF2AK3 (PERK). Downstream, it promotes chaperone expression and is essential for G-CSFR signaling and neutrophil elastase secretion. Disruption triggers XBP1 splicing, ATF4 translation, and DDIT3 (CHOP)-mediated apoptosis, highlighting its importance in ER proteostasis.
In HeLa cells, JAGN1 knockout disrupts ER stress signaling and secretory regulation, recapitulating molecular defects seen in severe congenital neutropenia (SCN). Although HeLa cells are non-hematopoietic, their conserved UPR machinery makes them a tractable system for studying JAGN1-dependent pathways. Loss of JAGN1 leads to aberrant ER morphology, altered chaperone expression, and impaired secretion, as evidenced by changes in HSPA5 and CHOP levels. This model bridges fundamental cell biology with disease mechanisms, offering insights into neutropenia pathogenesis and ER stress disorders.
These polyclonal cells are suitable for Western blotting of UPR markers (HSPA5, ATF4, CHOP), RT-qPCR for XBP1 splicing, immunofluorescence for ER morphology, and ELISA-based secretion assays. Applications include drug screening for ER stress modulators, phospho-signaling analysis of PERK/eIF2??, and apoptosis assays. The model also supports studies of secretory pathway dynamics and translational research into neutropenia therapies. For further information, please contact Ascent Research.
