MicroRNA sequence codes for small extracellular vesicle release and cellular retention

García‐Martín, Rubén; Wang, Guoxiao; Brandão, Bruna B.; Zanotto, Tamires M.; Shah, Samah; Patel, Shaunak; Schilling, Birgit; Kahn, C. Ronald

doi:10.1038/s41586-021-04234-3

Cited by 451 publications

(355 citation statements)

References 42 publications

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“…For all cell types, the obtained vesicles ranged in size between 50 and 200 nm, corresponding to exosome size, as measured by electron microscopy ( Figure 1B ). As we previously reported, the size distribution of the sEVs did not differ among the different cell types as measured by nanoparticle tracking analysis ( Garcia-Martin et al, 2021 ). The number of vesicles released by these cells into the culture medium over 48 h differed significantly among cell types.…”

Section: Resultssupporting

confidence: 71%

“…While work over the last decade has clearly established that the micro RNA (miRNA) cargo in sEV is regulated and cell type dependent ( Garcia-Martin et al, 2021 ; Valadi et al, 2007 ; Wei et al, 2017 ), less attention has been paid to how protein sorting into sEVs may differ among different cell types ( Angulski et al, 2017 ; Hoshino et al, 2015 ; Yoshioka et al, 2013 ). In the present study, we have used quantitative proteomics to compare the protein cargo of sEVs isolated from different cell lines representing the main tissues involved in metabolic disease, including white and brown adipocytes, muscle cells, hepatocytes, and endothelium, as well as differentiated murine stromal vascular fraction (SVF)-derived adipocytes.…”

Section: Introductionmentioning

confidence: 99%

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Tissue differences in the exosomal/small extracellular vesicle proteome and their potential as indicators of altered tissue metabolism

et al. 2022

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Section: Resultssupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Tissue differences in the exosomal/small extracellular vesicle proteome and their potential as indicators of altered tissue metabolism

et al. 2022

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“…Of note, miRNAs may affect gene expression not only in the cells they are produced, but also in distant cells and tissues through secreted extracellular vesicles, including exosomes ( 95 ). Importantly, small motifs in the miRNAs have recently been found to dictate their retention or secretion, with white adipocytes demonstrating by far the highest production and secretion rates per cell compared to several other cell types ( 96 ). Thus, future studies should be better equipped to predict and assess local and systemic effects of ER-regulated miRNAs.…”

Section: Mechanisms Of Action and Metabolic Regulation By Estrogen In...mentioning

confidence: 99%

Metabolic and Epigenetic Regulation by Estrogen in Adipocytes

et al. 2022

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Sex hormones contribute to differences between males and females in body fat distribution and associated disease risk. Higher concentrations of estrogens are associated with a more gynoid body shape and with more fat storage on hips and thighs rather than in visceral depots. Estrogen-mediated protection against visceral adiposity is shown in post-menopausal women with lower levels of estrogens and the reduction in central body fat observed after treatment with hormone-replacement therapy. Estrogen exerts its physiological effects via the estrogen receptors (ERα, ERβ and GPR30) in target cells, including adipocytes. Studies in mice indicate that estrogen protects against adipose inflammation and fibrosis also before the onset of obesity. The mechanisms involved in estrogen-dependent body fat distribution are incompletely understood, but involve, e.g., increased mTOR signaling and suppression of autophagy and adipogenesis/lipid storage. Estrogen plays a key role in epigenetic regulation of adipogenic genes by interacting with enzymes that remodel DNA methylation and histone tail post-translational modifications. However, more studies are needed to map the differential epigenetic effects of ER in different adipocyte subtypes, including those in subcutaneous and visceral adipose tissues. We here review recent discoveries of ER-mediated transcriptional and epigenetic regulation in adipocytes, which may explain sexual dimorphisms in body fat distribution and obesity-related disease risk.

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“…Short motifs have been identified in EV-sorted miRNAs (Garcia-Martin et al ., 2022; Santangelo et al ., 2016; Temoche-Diaz et al ., 2019) and mRNAs (Batagov and Kurochkin, 2013; Bolukbasi et al ., 2012; Szostak et al ., 2014). We therefore tested whether motifs found in EV-sorted mRNAs could be found in our robustly transferred mRNA cohort.…”

Section: Resultsmentioning

confidence: 99%

“…RNA motifs; Supplementary Figures 5 and 6, and Table 3) beyond gene expression is unlikely. Short motifs have been identified in EV-sorted miRNAs (Garcia-Martin et al ., 2022; Santangelo et al ., 2016; Temoche-Diaz et al ., 2019) and mRNAs (Batagov and Kurochkin, 2013; Bolukbasi et al ., 2012; Szostak et al ., 2014). Insertion of one such motif into a reporter RNA even influenced its recruitment into EVs (Szostak et al ., 2014).…”

Section: Discussionmentioning

confidence: 99%

Global analysis of human-to-mouse contact-dependent intercellular mRNA and lncRNA transfer in cell culture

Dasgupta

Dyagi

Haimovich

et al. 2021

Preprint

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SummaryFull-length mRNAs can transfer between adjacent mammalian cells via direct cell-to-cell connections called tunneling nanotubes (TNTs). However, the extent of mRNA transfer at the transcriptome-wide level (the transferome) is unknown. Here, we analyzed whole transcriptome mRNA transfer between heterogeneous human-mouse cell populations in in vitro co-culture using RNA-sequencing. Our data indicate that mRNA transfer is non-selective, prevalent across the human transcriptome, and that the amount of transfer to mouse embryonic fibroblasts (MEFs) strongly correlates with the endogenous level of gene expression in donor human breast cancer cells (MCF7). These results were validated by both quantitative RT-PCR and in situ hybridization, and analysis shows that typically <1% of endogenous mRNAs and lncRNAs undergo transfer. Non-selective expression-dependent RNA transfer was further validated using synthetic RNA reporters. Notably, significant differential changes in the native MEF transcriptome were observed in response to co-culture, including the upregulation of multiple cancer- and cancer-associated fibroblast-related genes and pathways. Together, these results lead us to suggest that TNT-mediated RNA transfer could be a phenomenon of physiological importance under both normal and pathogenic conditions.

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MicroRNA sequence codes for small extracellular vesicle release and cellular retention

Cited by 451 publications

References 42 publications

Tissue differences in the exosomal/small extracellular vesicle proteome and their potential as indicators of altered tissue metabolism

Tissue differences in the exosomal/small extracellular vesicle proteome and their potential as indicators of altered tissue metabolism

Metabolic and Epigenetic Regulation by Estrogen in Adipocytes

Global analysis of human-to-mouse contact-dependent intercellular mRNA and lncRNA transfer in cell culture

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