scholarly journals Differential detergent sensitivity of extracellular vesicle subpopulations

2015 ◽  
Vol 13 (38) ◽  
pp. 9775-9782 ◽  
Author(s):  
Xabier Osteikoetxea ◽  
Barbara Sódar ◽  
Andrea Németh ◽  
Katalin Szabó-Taylor ◽  
Krisztina Pálóczi ◽  
...  
Keyword(s):  
Extracellular Vesicle ◽  
Apoptotic Bodies ◽  
First Time

This work shows for the first time that exosomes are more resistant to detergents than microvesicles and apoptotic bodies.

scholarly journals Genome-wide interrogation of extracellular vesicle biology using barcoded miRNAs

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Albert Lu ◽  
Paulina Wawro ◽  
David W Morgens ◽  
Fernando Portela ◽  
Michael C Bassik ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Molecular Mechanisms ◽  
Membrane Vesicles ◽  
Extracellular Vesicle ◽  
Biologically Active ◽  
Vesicle Release ◽  
Guide Rnas ◽  
Disease States ◽  
Genome Wide ◽  
First Time

Extracellular vesicles mediate transfer of biologically active molecules between neighboring or distant cells, and these vesicles may play important roles in normal physiology and the pathogenesis of multiple disease states including cancer. However, the underlying molecular mechanisms of their biogenesis and release remain unknown. We designed artificially barcoded, exosomal microRNAs (bEXOmiRs) to monitor extracellular vesicle release quantitatively using deep sequencing. We then expressed distinct pairs of CRISPR guide RNAs and bEXOmiRs, enabling identification of genes influencing bEXOmiR secretion from Cas9-edited cells. This approach uncovered genes with unrecognized roles in multivesicular endosome exocytosis, including critical roles for Wnt signaling in extracellular vesicle release regulation. Coupling bEXOmiR reporter analysis with CRISPR-Cas9 screening provides a powerful and unbiased means to study extracellular vesicle biology and for the first time, to associate a nucleic acid tag with individual membrane vesicles.

scholarly journals INTEGRINS MEDIATE PLACENTAL EXTRACELLULAR VESICLE TRAFFICKING TO LUNG AND LIVER IN VIVO

2020 ◽  
Author(s):  
Sean L. Nguyen ◽  
Soo Hyun Ahn ◽  
Jacob W. Greenberg ◽  
Benjamin W. Collaer ◽  
Dalen W. Agnew ◽  
...  
Keyword(s):  
Immune Cells ◽  
Extracellular Vesicle ◽  
Dependent Manner ◽  
Cellular Phenotype ◽  
Reporter Mouse ◽  
Membrane Bound ◽  
First Time

ABSTRACTMembrane-bound extracellular vesicles (EVs) mediate intercellular communication in all organisms, and those produced by placental mammals have become increasingly recognized as significant mediators of fetal-maternal communication. Here, we aimed to identify maternal cells targeted by placental EVs and elucidate the mechanisms by which they traffic to these cells. Exogenously administered pregnancy-associated EVs traffic specifically to the lung; further, placental EVs associate with lung interstitial macrophages and liver Kupffer cells in an integrin-dependent manner. Localization of EV to maternal lungs was confirmed in unmanipulated pregnancy using a transgenic reporter mouse model, which also provided in situ and in vitro evidence that fetally-derived EVs, rarely, may cause genetic alteration of maternal cells. These results provide for the first time direct in vivo evidence for targeting of placental EVs to maternal immune cells, and further, evidence that EVs can alter cellular phenotype.

scholarly journals Extracellular Vesicles Hijack the Autophagic Pathway to Induce Tau Accumulation in Endolysosomes

2020 ◽  
Author(s):  
Giona Pedrioli ◽  
Marialuisa Barberis ◽  
Maurizio Molinari ◽  
Diego Morone ◽  
Stéphanie Papin ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Cell Model ◽  
Extracellular Vesicle ◽  
Clinical Progression ◽  
Cargo Delivery ◽  
Viable Solution ◽  
Associated Proteins ◽  
A Cell ◽  
Acidic Compartment ◽  
First Time

AbstractClinical progression of tauopathies is reflected by the transcellular propagation of pathogenic Tau seeds with the possible involvement of extracellular vesicles as transport vectors. However, the mechanism regulating extracellular vesicle cargo delivery to recipient cells is poorly understood. We established a cell model for investigating extracellular vesicle-delivery of membranes and proteins. In this model, extracellular vesicles are readily internalized and accumulate in endolysosomes. For the first time, we show that in this acidic compartment of recipient cells, extracellular vesicle-delivered Tau seeds cause the accumulation and abnormal folding of normal Tau by a process that requires the participation of autophagy. Endolysomes represent thus a cross-road where Tau seeds released from extracellular vesicles propagate on cellular Tau on its route for autophagy-mediated degradation, ultimately driving its accumulation, endolysosomal stress and cytotoxicity. Whilst, autophagy stimulation is considered as a viable solution to protect neurons from harmful cytosolic protein inclusions, our data suggest that this approach may favour the aberrant accumulation of neurodegeneration-associated proteins induced by exogenous pathogenic protein forms, with possible implications in the spreading of the disease.

scholarly journals A novel mechanism of generating extracellular vesicles during apoptosis via a beads-on-a-string membrane structure

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Georgia K. Atkin-Smith ◽  
Rochelle Tixeira ◽  
Stephanie Paone ◽  
Suresh Mathivanan ◽  
Christine Collins ◽  
...  
Keyword(s):  
Time Lapse ◽  
Extracellular Vesicle ◽  
Drug Screen ◽  
Membrane Protrusion ◽  
Apoptotic Bodies ◽  
String Structure ◽  
New Type ◽  
Sorting Process ◽  
String Membrane ◽  
Actomyosin Contraction

Abstract Disassembly of apoptotic cells into smaller fragments (a form of extracellular vesicle called apoptotic bodies) can facilitate removal of apoptotic debris and intercellular communication. However, the mechanism underpinning this process is unclear. While observing monocytes undergoing apoptosis by time-lapse microscopy, we discovered a new type of membrane protrusion that resembles a ‘beads-on-a-string’ structure. Strikingly, the ‘beads’ are frequently sheared off the ‘string’ to form apoptotic bodies. Generation of apoptotic bodies via this mechanism can facilitate a sorting process and results in the exclusion of nuclear contents from apoptotic bodies. Mechanistically, generation of ‘beads-on-a-string’ protrusion is controlled by the level of actomyosin contraction and apoptopodia formation. Furthermore, in an unbiased drug screen, we identified the ability of sertraline (an antidepressant) to block the formation of ‘beads-on-a-string’ protrusions and apoptotic bodies. These data uncover a new mechanism of apoptotic body formation in monocytes and also compounds that can modulate this process.

scholarly journals Brain-Derived Extracellular Vesicle microRNA Signatures Associated with In Utero and Postnatal Oxycodone Exposure

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 21 ◽  
Author(s):  
Farah Shahjin ◽  
Rahul S. Guda ◽  
Victoria L. Schaal ◽  
Katherine Odegaard ◽  
Alexander Clark ◽  
...  
Keyword(s):  
Brain Development ◽  
Cell Communication ◽  
Extracellular Vesicle ◽  
In Utero ◽  
Synaptic Function ◽  
Spine Density ◽  
Rna Seq ◽  
Membrane Bound ◽  
First Time

Oxycodone (oxy) is a semi-synthetic opioid commonly used as a pain medication that is also a widely abused prescription drug. While very limited studies have examined the effect of in utero oxy (IUO) exposure on neurodevelopment, a significant gap in knowledge is the effect of IUO compared with postnatal oxy (PNO) exposure on synaptogenesis—a key process in the formation of synapses during brain development—in the exposed offspring. One relatively unexplored form of cell–cell communication associated with brain development in response to IUO and PNO exposure are extracellular vesicles (EVs). EVs are membrane-bound vesicles that serve as carriers of cargo, such as microRNAs (miRNAs). Using RNA-Seq analysis, we identified distinct brain-derived extracellular vesicle (BDEs) miRNA signatures associated with IUO and PNO exposure, including their gene targets, regulating key functional pathways associated with brain development to be more impacted in the IUO offspring. Further treatment of primary 14-day in vitro (DIV) neurons with IUO BDEs caused a significant reduction in spine density compared to treatment with BDEs from PNO and saline groups. In summary, our studies identified for the first time, key BDE miRNA signatures in IUO- and PNO-exposed offspring, which could impact their brain development as well as synaptic function.

scholarly journals Differential Expression of Keratinocyte-Derived Extracellular Vesicle Mirnas Discriminate Exosomes From Apoptotic Bodies and Microvesicles

2018 ◽  
Vol 9 ◽  
Author(s):  
Uyen T.T. Than ◽  
Dominic Guanzon ◽  
James A. Broadbent ◽  
David I. Leavesley ◽  
Carlos Salomon ◽  
...  
Keyword(s):  
Differential Expression ◽  
Extracellular Vesicle ◽  
Apoptotic Bodies

scholarly journals Extracellular Vesicle Surface Signatures in IPF Patients: A Multiplex Bead-Based Flow Cytometry Approach

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1045
Author(s):  
Miriana d’Alessandro ◽  
Piera Soccio ◽  
Laura Bergantini ◽  
Paolo Cameli ◽  
Giulia Scioscia ◽  
...  
Keyword(s):  
Lung Diseases ◽  
Extracellular Vesicle ◽  
Interstitial Lung Diseases ◽  
Hazard Ratio ◽  
Term Survival ◽  
Antifibrotic Therapy ◽  
Kaplan Meier ◽  
Significant Difference ◽  
First Time ◽  
Multiplex Bead

Background: Extracellular vesicles (EVs) are secreted by cells from their membrane within circulation and body fluids. Knowledge of the involvement of EVs in pathogenesis of lung diseases is increasing. The present study aimed to evaluate the expression of exosomal surface epitopes in a cohort of idiopathic pulmonary fibrosis (IPF) patients followed in two Italian Referral Centres for Interstitial Lung Diseases, comparing them with a group of healthy volunteers. Materials and Methods: Ninety IPF patients (median age and interquartile range (IQR) 71 (66–75) years; 69 males) were selected retrospectively. Blood samples were obtained from patients before starting antifibrotic therapy. A MACSPlex Exosome Kit, human, (Miltenyi Biotec, Bergisch-Gladbach, Germany), to detect 37 exosomal surface epitopes, was used. Results: CD19, CD69, CD8, and CD86 were significantly higher in IPF patients than in controls (p = 0.0023, p = 0.0471, p = 0.0082, and p = 0.0143, respectively). CD42a was lower in IPF subjects than in controls (p = 0.0153), while CD209, Cd133/1, MCSP, and ROR1 were higher in IPF patients than in controls (p = 0.0007, p = 0.0050, p = 0.0139, and p = 0.0335, respectively). Kaplan-Meier survival analysis for IPF patients: for median values and a cut-off of 0.48 for CD25, the two subgroups showed a significant difference in survival rate (p = 0.0243, hazard ratio: 0.52 (95%CI 0.29–0.92); the same was true for CD8 (cut-off 1.53, p = 0.0309, hazard ratio: 1.39 (95%CI 0.75–2.53). Conclusion: Our multicenter study showed for the first time the expression of surface epitopes on EVs from IPF patients, providing interesting data on the communication signatures/exosomal profile in serum from IPF patients and new insights into the pathogenesis of the disease and a promising reliability in predicting mid-term survival of IPF patients.

scholarly journals Mechanisms of Extracellular Vesicle Biogenesis, Cargo Loading, and Release

2021 ◽  
Author(s):  
Abdel A. Alli
Keyword(s):  
Plasma Membrane ◽  
Circadian Rhythms ◽  
Nucleic Acids ◽  
Extracellular Vesicles ◽  
Extracellular Space ◽  
Extracellular Vesicle ◽  
Apoptotic Bodies ◽  
Endosomal Membranes ◽  
Vesicle Biogenesis

Extracellular vesicles (EVs) are carriers of various biomolecules including bioactive enzymes, lipids, proteins, nucleic acids, and metabolites. EVs are classified into three main types based on their size, biogenesis, and cargo. Exosomes originate from endosomal membranes and are the smallest type of EV. Microvesicles (MVs) or microparticles are larger in size, and like apoptotic bodies which represent the largest type of EVs, both of these vesicles originate from outward budding of the plasma membrane. As discussed in this chapter, cargo loading of EVs and their release into the extracellular space where they can be taken up by neighboring or distant cells plays an important role in physiology and pathophysiology. This chapter will outline specific mechanisms involved in the loading and enrichment of miRNAs, proteins, and lipids within EVs. As explained here, various external and biological stimuli play a role in EV release. Finally, recent studies have shown that the biogenesis, cargo loading, and release of EVs are governed by circadian rhythms. Although EVs were once thought to serve as garbage disposals of cells, the numerous roles they serve in physiology and pathophysiology are now being appreciated.

scholarly journals Integrins mediate placental extracellular vesicle trafficking to lung and liver in vivo

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sean L. Nguyen ◽  
Soo Hyun Ahn ◽  
Jacob W. Greenberg ◽  
Benjamin W. Collaer ◽  
Dalen W. Agnew ◽  
...  
Keyword(s):  
Immune Cells ◽  
Extracellular Vesicle ◽  
Dependent Manner ◽  
Cellular Phenotype ◽  
Reporter Mouse ◽  
Membrane Bound ◽  
First Time

AbstractMembrane-bound extracellular vesicles (EVs) mediate intercellular communication in all organisms, and those produced by placental mammals have become increasingly recognized as significant mediators of fetal-maternal communication. Here, we aimed to identify maternal cells targeted by placental EVs and elucidate the mechanisms by which they traffic to these cells. Exogenously administered pregnancy-associated EVs traffic specifically to the lung; further, placental EVs associate with lung interstitial macrophages and liver Kupffer cells in an integrin-dependent manner. Localization of EV to maternal lungs was confirmed in unmanipulated pregnancy using a transgenic reporter mouse model, which also provided in situ and in vitro evidence that fetally-derived EVs, rarely, may cause genetic alteration of maternal cells. These results provide for the first time direct in vivo evidence that placental EVs target maternal immune cells, and further, that EVs can alter cellular phenotype.

Annulate lamellae in the Sertoli cells of guinea pig testis after unilateral torsion of the spermatic cord

1984 ◽  
Vol 42 ◽  
pp. 196-197
Author(s):  
J. Chakraborty ◽  
A. P. Sinha Hikim ◽  
J. S. Jhunjhunwala
Keyword(s):  
Sertoli Cells ◽  
Guinea Pigs ◽  
Spermatic Cord ◽  
Present Report ◽  
Cell Types ◽  
Annulate Lamellae ◽  
Spermatogenic Cells ◽  
Electron Microscopic ◽  
Structural Details ◽  
First Time

Although the presence of annulate lamellae was noted in many cell types, including the rat spermatogenic cells, this structure was never reported in the Sertoli cells of any rodent species. The present report is based on a part of our project on the effect of torsion of the spermatic cord to the contralateral testis. This paper describes for the first time, the fine structural details of the annulate lamellae in the Sertoli cells of damaged testis from guinea pigs.One side of the spermatic cord of each of six Hartly strain adult guinea pigs was surgically twisted (540°) under pentobarbital anesthesia (1). Four months after induction of torsion, animals were sacrificed, testes were excised and processed for the light and electron microscopic investigations. In the damaged testis, the majority of seminiferous tubule contained a layer of Sertoli cells with occasional spermatogonia (Fig. 1). Nuclei of these Sertoli cells were highly pleomorphic and contained small chromatinic clumps adjacent to the inner aspect of the nuclear envelope (Fig. 2).

Sign in / Sign up

Export Citation Format

Share Document