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

Autor:	Donovan LJ; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA 94305, USA., Bridges CM; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA 94305, USA., Nippert AR; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA 94305, USA., Wang M; Stanford Center for Genomics and Personalized Medicine, Stanford University School of Medicine, Stanford, CA 94304, USA., Wu S; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA 94305, USA., Forman TE; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA 94305, USA., Haight ES; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA 94305, USA., Huck NA; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA 94305, USA., Bond SF; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA 94305, USA., Jordan CE; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA 94305, USA., Gardner AM; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA 94305, USA., Nair RV; Stanford Center for Genomics and Personalized Medicine, Stanford University School of Medicine, Stanford, CA 94304, USA., Tawfik VL; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA 94305, USA. Electronic address: vivianne@stanford.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2024 Feb 27; Vol. 43 (2), pp. 113683. Date of Electronic Publication: 2024 Jan 22.
DOI:	10.1016/j.celrep.2024.113683
Abstrakt:	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 of microglia to pain progression, we take advantage of a temporally controlled transgenic approach to transiently deplete microglia. Unexpectedly, we observe complete resolution of pain coinciding with microglial repopulation rather than depletion. We find that repopulated mouse spinal cord microglia are morphologically distinct from control microglia and exhibit a unique transcriptome. Repopulated microglia from males and females express overlapping networks of genes related to phagocytosis and response to stress. We intersect the identified mouse genes with a single-nuclei microglial dataset from human spinal cord to identify human-relevant genes that may ultimately promote pain resolution after injury. This work presents a comprehensive approach to gene discovery in pain and provides datasets for the development of future microglial-targeted therapeutics. Competing Interests: Declaration of interests The authors declare that they have no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu