Repopulated spinal cord microglia exhibit a unique transcriptome and contribute to pain resolution

• DOI: 10.1016/j.celrep.2024.113683
• Publication Date: 2024-01-22T17:43:46Z
• Authors: Lauren J. Donovan; Caldwell M. Bridges; Amy R. Nippert; Meng Wang; Shaogen Wu; Thomas E. Forman; Elena S. Haight; Nolan A. Huck; Sabrina F. Bond; Claire E. Jordan; Aysha M. Gardner; Ramesh V. Nair; Vivianne L. Tawfik
• Keywords: Male; 0303 health sciences; QH301-705.5; Pain; Article; Mice; 03 medical and health sciences; Spinal Cord; Phagocytosis; CP: Neuroscience; Humans; Animals; Female; Microglia; Biology (General); Transcriptome

Microglia are implicated as primarily detrimental in pain models; however, they exist across a continuum of states that contribute to homeostasis or pathology depending on timing and context. To clarify the specific contribution microglia progression, we take advantage temporally controlled transgenic approach transiently deplete microglia. Unexpectedly, observe complete resolution coinciding with microglial repopulation rather than depletion. We find repopulated mouse spinal cord morphologically distinct from control exhibit unique transcriptome. Repopulated males females express overlapping networks genes related phagocytosis response stress. intersect identified single-nuclei dataset human identify human-relevant may ultimately promote after injury. This work presents comprehensive gene discovery provides datasets for development future microglial-targeted therapeutics.