Peripheral nerve resident macrophages share tissue-specific programming and features of activated microglia
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ABSTRACT:
PROVIDER: PRJNA610789 | ENA |
REPOSITORIES: ENA
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Project description:Whereas microglia are recognized as fundamental players in central nervous system (CNS) development and function, much less is known about macrophages of the peripheral nervous system (PNS). Here, by comparing gene expression across neural and conventional tissue-resident macrophages, we identified transcripts that were shared among neural resident macrophages as well as selectively enriched in PNS macrophages. Remarkably, PNS macrophages constitutively expressed genes previously identified to be upregulated by activated microglia during aging, neurodegeneration, or loss of Sall1. Several microglial activation-associated and PNS macrophage-enriched genes were also expressed in spinal cord microglia at steady state. We further show that PNS macrophages rely on IL-34 for maintenance and arise from both embryonic and hematopoietic precursors, while their expression of activation-associated genes did not differ by ontogeny. Collectively, these data uncover shared and unique features between neural resident macrophages and emphasize the role of nerve environment for shaping PNS macrophage identity.
2020-06-01 | GSE146510 | GEO
Project description: Not available
| S-EPMC7242366 | biostudies-literature
Project description:The primary objective of this study was to compare global differences in transcriptional programming of resident and recruited alveolar macrophages in a time-limited murine model of lung inflammation. We first performed RNA sequencing of the resident and recruited alveolar macrophages from initiation through resolution of LPS-induced lung inflammation in the mouse. Our results indicate that despite existing in a shared environment, cell origin is the major determinant of programming of resident and recruited AMs during an acute inflammatory response. Major areas of difference include cell proliferation, inflammatory cytokine production and metabolism.
2017-09-19 | GSE94749 | GEO
Project description:microRNA transcriptome data from wild type and Gata6-deficient tissue resident peritoneal macrophages. Tissue resident macrophages are notoriously heterogeneous, exhibiting discrete phenotypes as a consequence of tissue- and micro-anatomical niche-specific functions, but the molecular basis for this is not understood. Gata6 itself has been shown to be a target of multiple miR. However, microRNA transcriptome and its dependence on tissue-specific macrophage programming, such as effected by GATA6, has not been explored. We used microRNA sequencing to determine the patterns of microRNA expression in peritoneal resident macrophages at homeostasis in the absence of GATA-6 against wild type.
2023-06-30 | E-MTAB-13039 | biostudies-arrayexpress
Project description:Tissue-resident macrophages are a diverse population of cells that perform specialized functions including sustaining tissue homeostasis and tissue surveillance. Here we report an interstitial subset of CD169+ lung-resident macrophages that are transcriptionally and developmentally distinct from alveolar macrophages (AMs). They are primarily localized around the airways and are found in close proximity to the sympathetic nerves located in the bronchovascular bundle. These nerve- and airway-associated macrophages (NAMs) are tissue-resident, yolk sac-derived, self-renewing, and do not require CCR2+ monocytes for development or maintenance. Unlike AMs, the development of NAMs requires CSF1, but not GM-CSF. Bulk population and single cell transcriptome analysis indicated that NAMs are distinct from other lung resident macrophage subsets and highly express immunoregulatory genes under steady state and inflammatory conditions. NAMs proliferated robustly following influenza infection and activation with the TLR ligand poly I:C, and in their absence, the inflammatory response was augmented resulting in excessive production of inflammatory cytokines and innate immune cell infiltration. Overall, our study provides insights into a distinct subset of airway-associated pulmonary macrophages that function to maintain immune and tissue homeostasis.
2020-03-10 | GSE146682 | GEO
Project description:Tissue-resident macrophages are a diverse population of cells that perform specialized functions including sustaining tissue homeostasis and tissue surveillance. Here we report an interstitial subset of CD169+ lung-resident macrophages that are transcriptionally and developmentally distinct from alveolar macrophages (AMs). They are primarily localized around the airways and are found in close proximity to the sympathetic nerves located in the bronchovascular bundle. These nerve- and airway-associated macrophages (NAMs) are tissue-resident, yolk sac-derived, self-renewing, and do not require CCR2+ monocytes for development or maintenance. Unlike AMs, the development of NAMs requires CSF1, but not GM-CSF. Bulk population and single cell transcriptome analysis indicated that NAMs are distinct from other lung resident macrophage subsets and highly express immunoregulatory genes under steady state and inflammatory conditions. NAMs proliferated robustly following influenza infection and activation with the TLR ligand poly I:C, and in their absence, the inflammatory response was augmented resulting in excessive production of inflammatory cytokines and innate immune cell infiltration. Overall, our study provides insights into a distinct subset of airway-associated pulmonary macrophages that function to maintain immune and tissue homeostasis.
2020-03-10 | GSE146681 | GEO
Project description:Framingham SHARe Social Network
| PRJNA75945 | ENA
Project description:Peripheral nerves provide a supportive growth environment for developing and regenerating axons and are essential for maintenance and repair of many non-neural tissues. This capacity has largely been ascribed to paracrine factors secreted by nerve-resident Schwann cells. Here, we used single-cell transcriptional profiling to identify ligands made by different injured rodent nerve cell types and have combined this with cell-surface mass spectrometry to computationally model potential paracrine interactions with peripheral neurons. These analyses show that peripheral nerves make many ligands predicted to act on peripheral and CNS neurons, including known and previously uncharacterized ligands. While Schwann cells are an important ligand source within injured nerves, more than half of the predicted ligands are made by nerve-resident mesenchymal cells, including the endoneurial cells most closely associated with peripheral axons. At least three of these mesenchymal ligands, ANGPT1, CCL11, and VEGFC, promote growth when locally applied on sympathetic axons. These data therefore identify an unexpected paracrine role for nerve mesenchymal cells and suggest that multiple cell types contribute to creating a highly pro-growth environment for peripheral axons.
2020-05-06 | GSE146883 | GEO
Project description:The resident astrocytes-retinal ganglion cell lipoxin circuit is impaired during retinal stress that include exocytotoxic- and ocular hypertension-induced neuropathy. Two endogenous lipoxins (Lipoxin A4 and Lipoxin B4) produced by homeostatic astrocytes directly act on RGCs. LXB4 is the most potent lipoxin in the retina and directly increases RGC survival and function in ocular hypertension-induced neuropathy. Homeostatic roles and cellular targets of LXB4 in the retina and optic nerve are a critical gap in knowledge. Single-cell RNA sequencing was used to define cellular targets and signaling of LXB4 in the retina. For modeling neurodegeneration, sustained ocular hypertension was induced by silicone-oil injection in the anterior chamber of mouse eyes. For morphological characterization of microglia populations in the retina and optic nerve, we used MorphOMICs and pseudotime trajectory analysis. Bulk RNA sequencing of optic nerves was performed to characterize pathways and mechanism of action for LXB4. qPCR and immunohistochemistry were used for validation of transcriptomics data. Student’s t-test and one-way ANOVA were used to determine differences between experimental groups. Single Cell transcriptomic identified microglia as a primary target for LXB4 in the healthy retina. LXB4 downregulated genes that drive microglia environmental sensing and reactivity responses. Analysis of microglia function uncovered that ocular hypertension induces distinct, temporally defined and dynamic phenotypes in the retina and, unexpectedly, in the distal myelinated optic nerve. Microglial expression of CD74, a marker of disease-associated microglia (DAM) in the brain, was only induced in a unique population of optic nerve microglia but not the retina. Genetic deletion of lipoxin formation correlated with presence of a CD74 optic nerve microglia population in normotensive eyes optic, while LXB4 treatment during ocular hypertension shifted optic nerve microglia toward a homeostatic morphology and non-reactive state and downregulated expression of CD74. Furthermore, we identified a correlation between CD74 and phospho-PI3K (p-PI3K) expression levels in the optic nerve, that was reduced by LXB4 treatment. Results identify distal optic nerve microglial dynamic and reactive responses as a key feature of ocular hypertension induce neurodegeneration. Our findings establish microglia regulation as a new LXB4 cell target in the retina and optic nerve. LXB4 maintenance of optic nerve microglia homeostatic phenotype and inhibition of a disease-associated phenotype are potential mechanisms for LXB4 neuroprotection.
2024-04-10 | GSE251716 | GEO