Visualizing Microglia with a Fluorescence Turn-On Ugt1a7c Substrate

Beomsue Kim1, Masahiro Fukuda2, Jung-Yeol Lee3,1,4

  • 1Singapore Bioimaging Consortium, Agency for Science Technology and Research (A*STAR), Singapore, 138667, Singapore.

Insights

Researchers developed CDr20, a novel fluorogenic chemical probe for visualizing microglia in the brain. This probe targets the Ugt1a7c enzyme, enabling fluorescence in microglia for advanced imaging applications.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Microglia, the brain's immune cells, are crucial for development and disease.
  • Current live microglia imaging is limited, primarily to transgenic models.
  • New methods for microglia detection and imaging are needed.

Purpose of the Study:

  • To develop a novel chemical probe for high-resolution imaging of live microglia.
  • To identify the molecular target of the developed probe.

Main Methods:

  • Structure-activity relationship studies to design the probe CDr20.
  • Genome-scale CRISPR-Cas9 knockout screening to identify the probe's target.
  • In vitro and in vivo imaging experiments.

Main Results:

  • CDr20, a high-performance fluorogenic chemical probe, was successfully developed.
  • UDP-glucuronosyltransferase Ugt1a7c was identified as the target of CDr20.
  • CDr20 enables visualization of microglia through Ugt1a7c-mediated glucuronidation.

Conclusions:

  • CDr20 facilitates non-invasive, cellular-resolution imaging of microglia in vitro and in vivo.
  • The discovery of Ugt1a7c as the target provides mechanistic insight into CDr20's function.
  • This probe represents a significant advancement for studying microglia in health and disease.

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