Unraveling the enigma: housekeeping gene Ugt1a7c as a universal biomarker for microglia

Front Psychiatry. 2024 Apr 11:15:1364201. doi: 10.3389/fpsyt.2024.1364201. eCollection 2024.

Abstract

Background: Microglia, brain resident macrophages, play multiple roles in maintaining homeostasis, including immunity, surveillance, and protecting the central nervous system through their distinct activation processes. Identifying all types of microglia-driven populations is crucial due to the presence of various phenotypes that differ based on developmental stages or activation states. During embryonic development, the E8.5 yolk sac contains erythromyeloid progenitors that go through different growth phases, eventually resulting in the formation of microglia. In addition, microglia are present in neurological diseases as a diverse population. So far, no individual biomarker for microglia has been discovered that can accurately identify and monitor their development and attributes.

Summary: Here, we highlight the newly defined biomarker of mouse microglia, UGT1A7C, which exhibits superior stability in expression during microglia development and activation compared to other known microglia biomarkers. The UGT1A7C sensing chemical probe labels all microglia in the 3xTG AD mouse model. The expression of Ugt1a7c is stable during development, with only a 4-fold variation, while other microglia biomarkers, such as Csf1r and Cx3cr1, exhibit at least a 10-fold difference. The UGT1A7C expression remains constant throughout its lifespan. In addition, the expression and activity of UGT1A7C are the same in response to different types of inflammatory activators' treatment in vitro.

Conclusion: We propose employing UGT1A7C as the representative biomarker for microglia, irrespective of their developmental state, age, or activation status. Using UGT1A7C can reduce the requirement for using multiple biomarkers, enhance the precision of microglia analysis, and even be utilized as a standard for gene/protein expression.

Keywords: UGT1A7C protein; biomarker; embryo development; housekeeping gene; microglial cell; mouse; neurologic disorders; transcriptome analysis.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by KBRI basic research program through Korea Brain Research Institute, funded by Ministry of Science and ICT (24-BR-01-03, 24-BR-03-04, and 24-BR-04-04), and by the Basic Science Research Program (NRF-2021R1A2C1013975) through the National Research Foundation of Korea to BK. The funders had no role in study design, data collection, analysis, publication decision, or manuscript preparation.