Visualizing Microglia with a Fluorescence Turn-On Ugt1a7c Substrate

  • Angew Chem Int Ed Engl. 2019 Jun 11;58(24):7972-7976. doi: 10.1002/anie.201903058.
Beomsue Kim  1 ,  Masahiro Fukuda  2 ,  Jung-Yeol Lee  3  1  4 ,  Dongdong Su  1 ,  Srikanta Sanu  1 ,  Aymeric Silvin  5 ,  Audrey T T Khoo  2 ,  Taejoon Kwon  6 ,  Xiao Liu  3  7 ,  Weijie Chi  8 ,  Xiaogang Liu  8 ,  Sejong Choi  9 ,  Diana S Y Wan  1 ,  Sung-Jin Park  1 ,  Jin-Soo Kim  10 ,  Florent Ginhoux  5 ,  H Shawn Je  2 ,  Young-Tae Chang  3  1  7
Affiliations
  • 1. Singapore Bioimaging Consortium, Agency for Science Technology and Research (A*STAR), Singapore, 138667, Singapore.
  • 2. Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore, 169857, Singapore.
  • 3. Department of Chemistry, Pohang University of Science and Technology, Pohang, 37673, Korea.
  • 4. Present address: New drug discovery center, DGMIF, Daegu, 41061, Korea.
  • 5. Singapore Immunology Network, A*STAR, Singapore, 138648, Singapore.
  • 6. Department of Biomedical Engineering, Ulsan National Institute of Science and Technology, Ulsan, 44919, Korea.
  • 7. Center for Self-assembly and Complexity, Institute for Basic Science (IBS), Pohang, 37673, Korea.
  • 8. Singapore University of Technology and Design, Singapore, 487372, Singapore.
  • 9. Department of Chemistry, Seoul National University, Seoul, 08826, Korea.
  • 10. Center for Genome Engineering, IBS, Daejeon, 34047, Korea.
PMID: 31038839 DOI: 10.1002/anie.201903058
Abstract

Microglia, the brain-resident macrophage, are involved in brain development and contribute to the progression of neural disorders. Despite the importance of microglia, imaging of live microglia at a cellular resolution has been limited to transgenic mice. Efforts have therefore been dedicated to developing new methods for microglia detection and imaging. Using a thorough structure-activity relationships study, we developed CDr20, a high-performance fluorogenic chemical probe that enables the visualization of microglia both in vitro and in vivo. Using a genome-scale CRISPR-Cas9 knockout screen, the UDP-glucuronosyltransferase Ugt1a7c was identified as the target of CDr20. The glucuronidation of CDr20 by Ugt1a7c in microglia produces fluorescence.

Keywords
biological activity; fluorescent probes; imaging agents; microglia; structure-activity relationships.
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