Evidence map›Paper›PMID 37546899›Full record

ArticlebioRxiv : the preprint server for biology2023

Identification of state-specific proteomic and transcriptomic signatures of microglia-derived extracellular vesicles.

Juliet V Santiago, Aditya Natu, Christina C Ramelow, Sruti Rayaprolu, Hailian Xiao, Vishnu Kumar, Nicholas T Seyfried, Srikant Rangaraju

Open access · greenAbstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 4 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Juliet V SantiagoDepartment of Neurology, Emory University, 201 Dowman Drive Atlanta, Georgia, 30322, United States of America.
Aditya NatuDepartment of Neurology, Emory University, 201 Dowman Drive Atlanta, Georgia, 30322, United States of America.
Christina C RamelowDepartment of Neurology, Emory University, 201 Dowman Drive Atlanta, Georgia, 30322, United States of America.
Sruti RayaproluDepartment of Neurology, Emory University, 201 Dowman Drive Atlanta, Georgia, 30322, United States of America.
Hailian XiaoDepartment of Neurology, Emory University, 201 Dowman Drive Atlanta, Georgia, 30322, United States of America.
Vishnu KumarDepartment of Neurology, Emory University, 201 Dowman Drive Atlanta, Georgia, 30322, United States of America.
Nicholas T SeyfriedDepartment of Neurology, Emory University, 201 Dowman Drive Atlanta, Georgia, 30322, United States of America.
Srikant RangarajuDepartment of Neurology, Emory University, 201 Dowman Drive Atlanta, Georgia, 30322, United States of America.
Emory University · US

Funding

Implementing a Maternal health and PRegnancy Outcomes Vision for Everyone (IMPROVE)UL1TR002378 · NCATS · EMORY UNIVERSITY · PI Andres J Garcia, Elizabeth O. Ofili · 2017 to 2026
$92.1M
Atlanta Clinical and Translational Science Institute (ACTSI) RenewalUL1TR000454 · NCATS · EMORY UNIVERSITY · PI STEPHENS, DAVID S · 2012 to 2016
$25.8M
Neuron and microglia-specific proteomic signatures of ERK mediated mechanisms of Alzheimer’s diseaseR01AG075820 · NIA · YALE UNIVERSITY · PI RANGARAJU, SRIKANT, SEYFRIED, NICHOLAS THOMAS · 2021 to 2025
$5.1M
Training In Systems And Integrative Biology NeuroscienceT32NS096050 · NINDS · EMORY UNIVERSITY · PI Yoland Smith · 2016 to 2026
$3.9M
Targeting Kv1.3 potassium channels for neuro-immunomodulation in Alzheimer's DiseaseR01NS114130 · NINDS · YALE UNIVERSITY · PI RANGARAJU, SRIKANT · 2020 to 2024
$3.1M
Microglia-specific proteomic mechanisms and biomarkers of neuroinflammation in Alzheimer’s diseaseRF1AG071587 · NIA · YALE UNIVERSITY · PI RANGARAJU, SRIKANT, SEYFRIED, NICHOLAS THOMAS · 2021 to 2021
$2.1M
FEI Transmission Electron Microscope with Tomography CapabilityS10RR025679 · NCRR · EMORY UNIVERSITY · PI SPEARMAN, PAUL W. · 2009 to 2009
$500k
Exosomes: A Novel Contributor of Microglia-Mediated Neuroinflammation and Neurodegeneration.F31NS127530 · NINDS · EMORY UNIVERSITY · PI SANTIAGO, JULIET VICTORIA · 2022 to 2023
$85k
NCATS NIH HHS UL1 TR000454NCATS NIH HHS UL1 TR002378NCRR NIH HHS S10 RR025679NIA NIH HHS R01 AG075820NIA NIH HHS RF1 AG071587NINDS NIH HHS F31 NS127530NINDS NIH HHS R01 NS114130NINDS NIH HHS T32 NS096050
6 · The paper itself

Abstract

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.

Indexed as

Extracellular vesiclesmass spectrometrymicroglianeuroinflammationproteomicsRNA sequencingtranscriptomics

Identifiers

PMID37546899
PMCPMC10402142
OpenAlexW4385375193

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.