한빛사 논문
Beomsue Kimb,†, Masahiro Fukudac,†, Jung-Yeol Leea,b,j, Dongdong Sub, Srikanta Sanub, Aymeric Silvind, Audrey T. T. Khooc, Taejoon Kwone, Xiao Liua,f,g, Weijie Chig, Xiaogang Liu, Sejong Choih, Diana S. Y. Wanb, Sung-Jin Parkb, Jin-Soo Kimi, Florent Ginhouxd, H. Shawn Jec,* and Young-Tae Changa,b,f,*
a Department of Chemistry, Pohang University of Science and Technology, Pohang 37673 (Korea)
b Singapore Bioimaging Consortium, Agency for Science Technology and Research (A*STAR), Singapore 138667 (Singapore)
c Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore 169857 (Singapore)
d Singapore Immunology Network, A*STAR, Singapore 138648 (Singapore)
e Department of Biomedical Engineering, Ulsan National Institute of Science and Technology, Ulsan 44919 (Korea)
f Center for Self-assembly and Complexity, Institute for Basic Science (IBS), Pohang 37673 (Korea)
g Singapore University of Technology and Design, Singapore 487372 (Singapore)
h Department of Chemistry, Seoul National University, Seoul 08826 (Korea)
iCenter for Genome Engineering, IBS, Daejeon 34047 (Korea)
j Present address: New drug discovery center, DGMIF, Daegu 41061 (Korea)
†These authors contributed equally to this work.
*To whom correspondence should be addressed.
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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