The HSP90AB1 Knockout HMC3 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human HMC3 microglial cell line, in which the HSP90AB1 gene has been disrupted to generate a loss-of-function model. This polyclonal population, produced via CRISPR/Cas9-mediated gene disruption, provides a heterogeneous mixture of knockout alleles, enabling the study of HSP90AB1-dependent functions without the clonal artifacts associated with single-cell-derived lines.
The parental HMC3 cell line is a well-characterized human microglial model originally derived from embryonic brain tissue. As resident immune cells of the central nervous system, HMC3 cells exhibit key microglial hallmarks, including immune surveillance, phagocytic activity, synaptic pruning capacity, and robust inflammatory cytokine secretion upon stimulation. They serve as a widely accepted in vitro platform for investigating neuroinflammatory mechanisms, microglial signaling, and glial cell biology.
HSP90AB1 encodes the beta isoform of heat shock protein 90, a ubiquitous molecular chaperone essential for the folding, stabilization, and activation of numerous client proteins. It functions within a multichaperone complex that includes co-chaperones such as CDC37, HOP/STIP1, AHA1, p23/PTGES3, and FKBP51, and interacts with HSP70 to facilitate client maturation. Key downstream targets include kinases (AKT, ERK, CDK4), transcription factors (p53, HIF-1??, STAT3), and signaling components (IKK complex). Consequently, HSP90AB1 acts as a hub for pathways like PI3K/AKT/mTOR, MAPK/ERK, NF-??B, JAK/STAT, and estrogen receptor signaling, regulating cell survival, proliferation, and stress responses.
In HMC3 microglia, disruption of HSP90AB1 leads to destabilization and degradation of client proteins, thereby impairing critical signaling cascades that govern inflammatory cytokine production, cell viability, and metabolic adaptation. For example, loss of HSP90AB1 attenuates NF-??B-driven transcription of pro-inflammatory cytokines such as TNF-?? and IL-6, while also diminishing AKT-mediated survival signals. This knockout model is thus a powerful tool for dissecting the chaperone-dependent regulation of microglial immune responses and for validating Hsp90 inhibitors in a neuroinflammatory context.
Typical experimental applications include investigating the role of HSP90AB1 in microglial activation and neuroinflammation, assessing client protein stability via western blotting and co-immunoprecipitation, profiling changes in phospho-signaling networks with flow cytometry, and measuring cytokine secretion by ELISA. The polyclonal nature of the knockout population facilitates pooled functional screens and RNA-seq-based transcriptomic analyses, avoiding clonal bias. For further information or to request a quote, please contact Ascent Research.
