Similar Datasets
Project description:The RNA sequencing of microglia repopulated retina
| PRJNA414904 | ENA
Project description:Microglia contribute to the initiation of pain, however, a translationally viable approach addressing how or when to modulate these cells remains elusive. We used a targeted, inducible, genetic microglial depletion strategy at both acute and acute-to-chronic transition phases in the clinically-relevant tibial fracture/casting pain model to determine the contribution of microglia to the initiation and maintenance of pain. We observed complete resolution of pain which coincided with the timeframe of full repopulation of microglia after transient microglial depletion at the acute-to-chronic phase. These repopulated microglia were morphologically distinct from control microglia, signifying they may exhibit a unique transcriptome. RNA sequencing of repopulated spinal cord microglia identified genes of interest using weighted gene coexpression network analysis (WGCNA). We intersected these genes with a newly generated single nuclei microglial dataset from human spinal cord dorsal horn and identified human-relevant genes that may ultimately promote pain resolution after injury. This work presents a novel approach to gene discovery in pain and provides comprehensive datasets for the development of future microglial-targeted therapeutics.
2023-12-04 | GSE249210 | GEO
Project description:Microglia contribute to the initiation of pain, however, a translationally viable approach addressing how or when to modulate these cells remains elusive. We used a targeted, inducible, genetic microglial depletion strategy at both acute and acute-to-chronic transition phases in the clinically-relevant tibial fracture/casting pain model to determine the contribution of microglia to the initiation and maintenance of pain. We observed complete resolution of pain which coincided with the timeframe of full repopulation of microglia after transient microglial depletion at the acute-to-chronic phase. These repopulated microglia were morphologically distinct from control microglia, signifying they may exhibit a unique transcriptome. RNA sequencing of repopulated spinal cord microglia identified genes of interest using weighted gene coexpression network analysis (WGCNA). We intersected these genes with a newly generated single nuclei microglial dataset from human spinal cord dorsal horn and identified human-relevant genes that may ultimately promote pain resolution after injury. This work presents a novel approach to gene discovery in pain and provides comprehensive datasets for the development of future microglial-targeted therapeutics.
2023-12-05 | GSE248983 | GEO
Project description:Microglia contribute to the initiation of pain, however, a translationally viable approach addressing how or when to modulate these cells remains elusive. We used a targeted, inducible, genetic microglial depletion strategy at both acute and acute-to-chronic transition phases in the clinically-relevant tibial fracture/casting pain model to determine the contribution of microglia to the initiation and maintenance of pain. We observed complete resolution of pain which coincided with the timeframe of full repopulation of microglia after transient microglial depletion at the acute-to-chronic phase. These repopulated microglia were morphologically distinct from control microglia, signifying they may exhibit a unique transcriptome. RNA sequencing of repopulated spinal cord microglia identified genes of interest using weighted gene coexpression network analysis (WGCNA). We intersected these genes with a newly generated single nuclei microglial dataset from human spinal cord dorsal horn and identified human-relevant genes that may ultimately promote pain resolution after injury. This work presents a novel approach to gene discovery in pain and provides comprehensive datasets for the development of future microglial-targeted therapeutics.
2023-06-09 | GSE234081 | GEO
Project description:The RNA sequencing of brain after microglial depletion and repopulation
2018-02-24 | GSE108269 | GEO
Project description:To probe potential molecular mechanisms underlying the differences between wild-type and Hk2-cKO microglia during repopulation, we performed the single-cell RNA sequencing (scRNA-seq) of repopulated microglia at Day 3. Microglia were isolated by FACS as CD11b high CD45 low cells from normal brains and Hk2-cKO brains.
2021-12-17 | GSE188642 | GEO
Project description:The RNA sequencing of brain after microglial depletion and repopulation
| PRJNA423014 | ENA
Project description:Cx3cr1CreER-Eyfp/wt mice contain a subset of microglia lacking Cre and EYFP expression. These microglial escape Cre-mediated recombination and gain a repopulation advantage following Cre-driven DTA-mediated microglial depletion.
2022-02-01 | GSE186700 | GEO
Project description:Diabetic retinopathy, a microvascular disease characterized by irreparable vascular damage, neurodegeneration and neuroinflammation, is a leading complication of diabetes mellitus. Medical interventions slow the progression of disease. However, current therapies do not specifically target microglia, a cell type implicated in mediating disease development. Microglia-mediated inflammation in the diabetic retina is regulated via CX3CR1-FKN signaling, where FKN serves as a dampening signal for microglial activation. Studying this signaling axis is important as polymorphic variants of CX3CR1 are found in 25% of the human population, hCX3CR1I249/M280, resulting in a receptor with lower binding affinity for FKN. Furthermore, disrupted CX3CR1-FKN signaling in CX3CR1-KO and FKN-KO mice leads to exacerbated microglial activation, robust neuronal cell loss and substantial vascular damage in the diabetic retina. Thus, studies to characterize the effects of hCX3CR1I249/M280-expression in microglia-mediated inflammation in the diseased retina are potentially clinically relevant to identify microglia-specific therapies. Our results show that hCX3CR1I249/M280 mice are significantly more susceptible to microgliosis and production of Cxcl10 and TNFα under acute inflammatory conditions. This pathology is exacerbated under diabetic conditions and coincides with robust neuronal loss in comparison to CX3CR1-WT mice. Therefore, to further investigate the role of hCX3CR1I249/M280-expression in microglial responses, we pharmacologically depleted microglia using PLX-5622, a CSF-1R antagonist. PLX-5622 treatment led to a robust (~70%) reduction in Iba1+ microglia in all non-diabetic and diabetic mice. CSF-1R antagonism in diabetic CX3CR1-WT prevented TUJ1+ axonal loss, angiogenesis and fibrinogen deposition. In contrast, PLX-5622 microglia depletion in CX3CR1-KO and hCX3CR1I249/M280 mice did not alleviate TUJ1+ axonal loss or angiogenesis. Interestingly, PLX-5622 treatment reduced fibrinogen deposition in CX3CR1-KO mice but not in hCX3CR1I249/M280 mice, revealing that hCX3CR1I249/M280 receptor variant mice behave differently in terms of vascular pathology compared to CX3CR1-KOs. mRNAseq gene expression analysis in CX3CR1-WT retinal isolates revealed that PLX-5622-induced microglia depletion and repopulation induced a downregulation in genes associated with microglial activation and phagocytosis, B2m, Cx3cr1, and Trem2, and complement-associated synaptic pruning, C1qa, C1qb, and C1qc. Furthermore, mRNAseq analysis of PLX-5622 treated CX3CR1-WT retinas showed lower fold changes in genes encoding proinflammatory mediators (Cxcl10, Ccl2, Il6, Cxcl1, Selp, Il12b, Tnf, Cxcl2, Icam1 and Vcam1) in comparison to diabetic + normal chow mice.
2023-01-28 | GSE223522 | GEO
Project description:Microglia are suspected to be a key player in several neurological diseases. Here, we investigated whether microglia depletion affects dendritic spine density after short-term microglia depletion with subsequent repopulation in the adult mouse brain.
2024-05-06 | GSE220141 | GEO