Proteomic analysis of cerebrospinal fluid extracellular vesicles: A comprehensive dataset

Chiasserini, Davide; Weering, Jan R.T. van; Piersma, Sander R.; Pham, Thang V.; Malekzadeh, Arjan; Teunissen, Charlotte E.; Wit, Heidi de; Jiménez, Connie R.

doi:10.1016/j.jprot.2014.04.028

Cited by 215 publications

(185 citation statements)

References 59 publications

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“…The significance of hnRNPA2/B1 within CSF vesicles is likely the transport of cellular miRNAs into EVs, although further studies will be needed to address this hypothesis. Our findings that hnRNPA2/B1 may have an important function in CSF EVs are supported by a recent proteomic study has also indicated that many hnRNPs including hnRNPA2/B1 are present in CSF EVs [21]. In conclusion, the temporal dynamics of CSF EV concentrations and miRNA content likely play an important role in coordinating intercellular and intracellular communication in brain development.…”

Section: Discussionsupporting

confidence: 87%

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Cerebrospinal Fluid Extracellular Vesicles Undergo Age Dependent Declines and Contain Known and Novel Non-coding RNAs

Tietje

Wei

et al. 2014

PLoS ONE

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Brain development requires precise orchestration of cellular events through the coordinate exchange of information between distally located cells. One mechanism by which intercellular communication is achieved is through the transfer of extracellular vesicles (EVs). Exosomes are EVs that carry lipids, nucleic acids, and proteins and are detectable in most biological fluids including cerebrospinal fluid (CSF). Here we report that CSF EV concentrations undergo age dependent fluctuations. We characterized EV RNA content by next generation small RNA sequencing and miRNA microarray analysis and identified a temporal shift in CSF EV content. CSF EVs encapsulated miRNAs that contain a conserved hnRNPA2/B1 recognition sequence. We found that hnRNPA2/B1-containing EVs were produced by choroid plexus epithelial cells and that hnRNPA2/B1 containing EVs decreased with age. These results provide insight into EV exchange of miRNAs within the central nervous system and a framework to understand how changes in EVs may have an important impact on brain development.

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Section: Discussionsupporting

confidence: 87%

“…EVs are detectable in most biological fluids including CSF [5], [15]–[21]. CSF EVs encapsulate miRNA during embryonic development in rodents and humans and may promote neural stem cell (NSC) amplification [5].…”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal Fluid Extracellular Vesicles Undergo Age Dependent Declines and Contain Known and Novel Non-coding RNAs

Tietje

Wei

et al. 2014

PLoS ONE

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“…Instead, NPR may reach the periphery in a membrane-bound form. Although exosomes, which can cross the blood-brain barrier and represent a potential clearance mechanism for degraded proteins (Kalani et al, 2014) might be considered for this role, recent proteomic characterization of CSF suggests relative depletion rather than enrichment of NPR in extracellular vesicular fractions (Chiasserini et al, 2014). …”

Section: Discussionmentioning

confidence: 99%

Parallel age-associated changes in brain and plasma neuronal pentraxin receptor levels in a transgenic APP/PS1 rat model of Alzheimer's disease

Bilousova

Taylor

Emirzian

et al. 2015

Neurobiology of Disease

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Neuronal pentraxin receptor (NPR) is a synaptic protein implicated in AMPA receptor trafficking at excitatory synapses. Since glutamate neurotransmission is disrupted in Alzheimer’s disease (AD), NPR levels measured from plasma represent a potential biomarker for synaptic dysfunction associated with AD. We sought to determine the relationship between AD pathology and brain and plasma NPR levels by examining age-associated NPR levels in these compartments in a transgenic APP/PS1 rat model of AD. NPR levels in cortical homogenate were similar in wild-type (Wt) and APP/PS1 rats at 3 months of age (prior to Aβ plaque deposition), but significantly increased in APP/PS1 rats by 9 and 18-20 months of age (after the onset of plaque deposition). These age-dependent differences were driven by proportional increases in NPR in membrane-associated cortical fractions. Genotype-related differences in NPR expression were also seen in the hippocampus, which exhibits significant Aβ pathology, but not in the cerebellum, which does not. Plasma analyses revealed increased levels of a 26 kDa NPR fragment in APP/PS1 rats relative to Wt rats by 18-20 months of age, which correlated with the levels of full-length NPR in cortex. Our findings indicate that cerebral accumulation of NPR and Aβ occurs with similar temporal and regional patterns in the APP/PS1 model, and suggest that a 26 kDa plasma NPR fragment may represent a peripheral biomarker of this process.

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“…Extracellular Vesicle Preparation by Ultracentrifugation-Extracellular vesicle preparation by differential ultracentrifugation was performed as described previously (36,37). Cells were washed twice in cold serum-free IMDM (Gibco) and resuspended in IMDM (lacking phenol red) at a cell density of 2 ϫ 10 6 /ml.…”

Section: Methodsmentioning

confidence: 99%

“…Next, we used differential centrifugation to isolate EVs from the secretome derived from selected patient specimens. The purity of vesicle preparation using this protocol was previously demonstrated (36,37). Proteins isolated from EVs were analyzed by gel-LC-MS/MSbased proteomics.…”

Section: The Secretome Of Apoptosis-resistant Aml Blasts Contains Promentioning

confidence: 99%

Exosomes Secreted by Apoptosis-Resistant Acute Myeloid Leukemia (AML) Blasts Harbor Regulatory Network Proteins Potentially Involved in Antagonism of Apoptosis

Wojtuszkiewicz

Schuurhuis

Kessler

et al. 2016

Molecular & Cellular Proteomics

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myeloid leukemia (AML) blasts at diagnosis is associated with disease-free survival. We previously found that the initially high apoptosis-resistance of AML cells decreased after therapy, while regaining high levels at relapse. Herein, we further explored this aspect of dynamic apoptosis regulation in AML. First, we showed that the intraindividual ex vivo apoptosis-related profiles of normal lymphocytes and AML blasts within the bone marrow of AML patients were highly correlated. The expression values of apoptosisregulating proteins were far beyond healthy control lymphocytes, which implicates the influence of microenvironmental factors. Second, we demonstrated that apoptosis-resistant primary AML blasts, as opposed to apoptosis-sensitive cells, were able to up-regulate BCL-2 expression in sensitive AML blasts in contact cultures (p ‫؍‬ 0.0067 and p ‫؍‬ 1.0, respectively). Using secretome proteomics, we identified novel proteins possibly engaged in apoptosis regulation. Intriguingly, this analysis revealed that major functional protein clusters engaged in global gene regulation, including mRNA splicing, protein translation, and chromatin remodeling, were more abundant (p ‫؍‬ 4.01E-06) in secretomes of apoptosis-resistant AML. These findings were confirmed by subsequent extracellular vesicle proteomics. Despite good remission rates observed in acute myeloid leukemia (AML) patients, the 5-year event-free survival rates reach only 35-40% in adults and 60 -70% in children (1, 2). Apoptosis is one of the crucial mechanisms influencing survival of AML cells, and its deregulation can possibly lead to chemotherapy resistance and eventually relapse (3-5). The ability of cells to undergo apoptosis is largely defined by the relative expression of anti-(i.e. BCL-2, BCL-X long isoform -BCL-XL, or MCL-1) and proapoptotic (i.e. BAX, BH3 interacting domain death agonist -BID, caspases) proteins. Several studies have shown that the levels of BCL-2 and BCL-2/BAX ratio are a determinant of apoptosis-resistance in AML blasts and are associated with survival in AML patients (3,6). We have previously demonstrated that the expression of several apoptosis-related proteins, such as BCL-2, BCL-XL, MCL-1, From the ‡Dept.

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Proteomic analysis of cerebrospinal fluid extracellular vesicles: A comprehensive dataset

Cited by 215 publications

References 59 publications

Cerebrospinal Fluid Extracellular Vesicles Undergo Age Dependent Declines and Contain Known and Novel Non-coding RNAs

Cerebrospinal Fluid Extracellular Vesicles Undergo Age Dependent Declines and Contain Known and Novel Non-coding RNAs

Parallel age-associated changes in brain and plasma neuronal pentraxin receptor levels in a transgenic APP/PS1 rat model of Alzheimer's disease

Exosomes Secreted by Apoptosis-Resistant Acute Myeloid Leukemia (AML) Blasts Harbor Regulatory Network Proteins Potentially Involved in Antagonism of Apoptosis

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