Dissecting the Role of Mertk in Trigeminal Ganglia from Nitroglycerin-Induced Mouse Pain Model Using Single-Cell RNA Sequencing

Sun Young Kim (Advisor: Seung-Hee Yoo, PhD)

          Cluster headache (CH) is a highly debilitating primary headache disorder that affects 0.1% of the global population. Emerging studies suggest that CH displays pronounced circadian rhythmicity in CH attacks. Recent genome-wide association studies have identified MERTK as a susceptibility gene linked to CH. We recently revealed that Mertk plays a pivotal role in maintaining cellular homeostasis and coordinating intercellular networks within the trigeminal ganglion (TG), thereby contributing to chronic Nitroglycerin (NTG)-induced hypersensitivity. Using single-cell RNA sequencing datasets, my analysis revealed that Mertk is primarily expressed in satellite glial cells, endothelial cells, and myofibroblasts in the TG. Furthermore, Mertk KO mice demonstrated widespread remodeling of the neuronal landscape compared to wild-type mice, accompanied by decreased Bax mRNA expression. Finally, I found that multiple signaling pathways (e.g., the galectin, neuregulin, and ICAM pathways) within the intercellular communication network were altered in Mertk KO mice. These transcriptomic datasets provide a compelling molecular gateway toward understanding the pain behavior phenotype observed in Mertk KO mice.

Advisory Committee:

• Seung-Hee Yoo, PhD, Chair
• Mark J. Burish, MD, PhD
• Zheng Chen, PhD
• Goo Jun, PhD
• Kristin Eckel Mahan, PhD