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Class switch recombination regulation by extracellular vesicles mediated intercellular epigenomic signaling

ABSTRACT: B cell maturation is crucial for effective adaptive immunity and requires a complex signaling network to control gene expression and protein function to mediate antibody diversification. B cells also rely on extracellular signaling queues from other cells within the germinal center. Recently, a novel class of intercellular signaling mediated by extracellular vesicles (EVs) has emerged. Studies have shown B cell EVs mediated signaling is involved in immune response regulation, infection control, and tumorigenesis. However, the mechanistic role of B cell EVs in B cell maturation is not yet established. We herein study the biological properties and physiological function of B cell EVs in the context of B cell maturation. We use novel technologies to characterize B cell EVs surface marker signatures, molecular cargo and physiological roles in B cell maturation. A new specialized nanoparticle analyzer was used to profile B cell EVs at the single particle level and characterize their surface markers and sub-populations at various maturation stages. EV ncRNA cargo was characterized by RNA-seq and bioinformatic analyses identified an EVs mediated regulatory network for B cell maturation. A previously uncharacterized micro-RNA (miR-5099) in combination with a set of long non-coding RNA carried within B cell EVs is shown to be important for antibody diversification signaling. The physiological role of EVs in B cell maturation is investigated using EV blockade assays and complementation studies using diverse EV sources further confirmed the physiological role and mode of action of EVs in B cell maturation.

ORGANISM(S): Mus musculus

PROVIDER: GSE242731 | GEO | 2025/02/05

REPOSITORIES: GEO

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Osteoblasts secrete miRNA-containing extracellular vesicles that enhance expansion of human umbilical cord blood cells

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2016-10-05 | E-MTAB-4560 | biostudies-arrayexpress

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2022-10-30 | GSE216498 | GEO

Crosstalk between the effects of extracellular vesicles (Evs) and TNF on U937 human monocyte cell line

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2021-04-29 | GSE173474 | GEO

Small RNA profiles of follicular fluid-derived small extracellular vesicles

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2023-06-22 | GSE221271 | GEO

Acute Resistance Exercise Modifies Extracellular Vesicle miRNAs Targeting Anabolic Gene Pathways: A Prospective Cohort Study

Project description:BACKGROUND: Resistance training confers numerous health benefits that are mediated in part by circulating factors. Towards an enhanced molecular understanding, there is growing interest in a class of signaling biomarkers called extracellular vesicles (EVs). Extracellular vesicles support physiological adaptations to exercise by transporting their cargo (e.g., microRNA [miRNA]) to target cells. Previous studies of changes in EV cargo have focused on aerobic exercise, with limited data examining the effects of resistance exercise. We examined the effect of acute resistance exercise on circulating EV miRNAs and their predicted target pathways. METHODS: Ten participants (5 men; age: 26.9±5.5 y, height: 1.7±0.1 m, body mass: 74.0±11.1 kg, body fat: 25.7±11.6 %) completed an acute heavy resistance exercise test (AHRET) consisting of six sets of 10 repetitions of back squats using 75% one-repetition maximum. Pre-/post-AHRET, EVs were isolated from plasma using size exclusion chromatography, and RNA sequencing was performed. Differentially expressed (DE) miRNAs between pre- and post-AHRET EVs were analyzed using Ingenuity Pathway Analysis to predict target messenger RNAs and their target biological pathways. RESULTS: Overall, 34 miRNAs were altered by AHRET (p<0.05), targeting 4,895 mRNAs, with enrichment of 175 canonical pathways (p<0.01), including 12 related to growth/metabolism (p53, IGF-I, STAT3, PPAR, JAK/STAT, growth hormone, WNT/β-catenin, ERK/MAPK, AMPK, mTOR, and PI3K/AKT) and eight to inflammation signaling (TGF-β, IL-8, IL-7, IL-3, IL-6, IL-2, IL-17, IL-10). CONCLUSION: Acute resistance exercise alters EV miRNAs targeting pathways involved in growth, metabolism, and immune function. Circulating EVs may serve as significant adaptive signaling molecules influenced by exercise training.

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Extracellular vesicles isolated from human induced pluripotent stem cell-derived neurons contain a transcriptional network

Project description:Healthy brain function is mediated by several complementary signalling pathways, many of which are driven by extracellular vesicles (EVs). EVs are heterogeneous in both size and cargo and are constitutively released from cells into the extracellular milieu. They are subsequently trafficked to recipient cells, whereupon their entry can modify the cellular phenotype. Here, in order to further analyse the mRNA and protein cargo of neuronal EVs, we isolated EVs by size exclusion chromatography from human induced pluripotent stem cell (iPSC)-derived neurons. Electron microscopy and dynamic light scattering revealed that the isolated EVs had a diameter of 30-100 nm. Transcriptomic and proteomics analyses of the EVs and neurons identified key molecules enriched in the EVs involved in cell surface interaction (integrins and collagens), internalisation pathways (clathrin- and caveolin-dependent), downstream signalling pathways (phospholipases, integrin-linked kinase and MAPKs), and long-term impacts on cellular development and maintenance. Overall, we show that key signalling networks and mechanisms are enriched in EVs isolated from human iPSC-derived neurons.

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