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Updated: Sep 4, 2026

Dissection of Enhancer Function Using Multiplex CRISPR-based Enhancer Interference in Cell Lines
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Functional and Multi-Omics Effects of an Optimized CRISPR-Mediated FURIN Depletion in U937 Monocytes

Ruiming Chua1, Lijin Wang2, Roshni Singaraja3

  • 1Program in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, Singapore 169857, Singapore.

Cells
|April 12, 2024
PubMed

Insights

FURIN (PCSK3) inhibition in myeloid cells impacts functions like phagocytosis and migration. This research offers insights into FURIN

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cardiovascular Research

Background:

  • Pro-protein convertase FURIN (PCSK3) plays a role in various diseases, including cardiovascular disorders.
  • Previous studies showed FURIN inhibition reduces atherosclerotic plaques and alters macrophage function.

Purpose of the Study:

  • To investigate the cellular mechanisms of FURIN inhibition in myeloid cells.
  • To establish FURIN knockout models in U937 monocytic cells for functional analysis.

Main Methods:

  • Optimized CRISPR-mediated gene deletion for hemizygous (HZ) and nullizygous (NZ) FURIN knockout U937 clones.
  • Utilized lipotransfection and dual guide RNA delivery.
  • Analyzed differences in myeloid cell functions between wild-type, HZ, and NZ FURIN clones.

Main Results:

  • Observed functional differences in monocytes and macrophages related to phagocytosis, lipid accumulation, and migration.
  • Detected alterations in inflammatory gene expression and cytokine release patterns.
  • Identified changes in secreted proteomics and whole-genome transcriptomics.

Conclusions:

  • Myeloid cell FURIN plays a significant role in cellular functions relevant to cardiovascular disorders.
  • These findings provide a mechanistic basis for targeting FURIN in cardiovascular disease.
Keywords:
FURIN proteasecytokine secretionfunctional assaysgene editinggenomicsmyeloid cells

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