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| Status |
Public on Aug 12, 2023 |
| Title |
Identification of state-specific proteomic and transcriptomic signatures of microglia-derived extracellular vesicles [bulk rna-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Microglia are resident immune cells of the brain that play important roles in mediating inflammatory responses in several neurological diseases via direct and indirect mechanisms. One indirect mechanism may involve extracellular vesicle (EV) release, so that the molecular cargo transported by microglia-derived EVs can have functional effects by facilitating intercellular communication. The molecular composition of microglia-derived EVs, and how microglial activation states impacts EV composition and EV-mediated effects in neuroinflammation, remain poorly understood. We hypothesize that microglia-derived EVs have unique molecular profiles that are determined by microglial activation state. Using size-exclusion chromatography to purify EVs from BV2 microglia, combined with proteomic (label-free quantitative mass spectrometry or LFQ-MS) and transcriptomic (mRNA and non-coding RNA seq) methods, we obtained comprehensive molecular profiles of microglia-derived EVs. LFQ-MS identified several classic EV proteins (tetraspanins, ESCRT machinery, and heat shock proteins), in addition to over 200 proteins not previously reported in the literature. Unique mRNA and microRNA signatures of microglia-derived EVs were also identified. After treating BV2 microglia with lipopolysaccharide (LPS), interleukin-10, or transforming growth factor beta, to mimic pro-inflammatory, anti-inflammatory, or homeostatic states, respectively, LFQ-MS and RNA seq revealed novel state-specific proteomic and transcriptomic signatures of microglia-derived EVs. Particularly, LPS treatment had the most profound impact on proteomic and transcriptomic compositions of microglia-derived EVs. Furthermore, we found that EVs derived from LPS-activated microglia were able to induce pro-inflammatory transcriptomic changes in resting responder microglia, confirming the ability of microglia-derived EVs to relay functionally-relevant inflammatory signals. These comprehensive microglia-EV molecular datasets represent important resources for the neuroscience and glial communities, and provide novel insights into the role of microglia-derived EVs in neuroinflammation.
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| Overall design |
We equally dosed individual wells of BV2 cells with EVs secreted from control and LPS treated BV2 cells to assess gene expression changes in recipient microglia using RNA sequencing. Resting microglia were treated with extracellular vesicles for 24 hours.
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| Contributor(s) |
Santiago JV, Natu A, Ramelow CC, Rayaprolu S, Xiao H, Kumar V, Seyfried NT, Rangaraju S |
| Citation(s) |
37546899, 37952696 |
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| Submission date |
Aug 07, 2023 |
| Last update date |
Jan 03, 2024 |
| Contact name |
Srikant Rangaraju |
| E-mail(s) |
Srikant.rangaraju@emory.edu
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| Organization name |
Emory University
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| Department |
Neurology
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| Street address |
615 Michael St
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| City |
Atlanta |
| State/province |
GA |
| ZIP/Postal code |
30322 |
| Country |
USA |
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| Platforms (1) |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE240295 |
Identification of state-specific proteomic and transcriptomic signatures of microglia-derived extracellular vesicles |
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| Relations |
| BioProject |
PRJNA1003104 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE240290_IL10_BulkRNAseq_Responder_Cells_Processed_Data.csv.gz |
384.0 Kb |
(ftp)(http) |
CSV |
| GSE240290_LPS_BulkRNAseq_Responder_Cells_Cleandat.csv.gz |
382.8 Kb |
(ftp)(http) |
CSV |
| GSE240290_LPS_BulkRNAseq_Responder_Cells_Processed_Data.csv.gz |
382.8 Kb |
(ftp)(http) |
CSV |
| GSE240290_TGFB_BulkRNAseq_Responder_Cells_Processed_Data.csv.gz |
381.8 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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