Abstract Extracellular matrix (ECM) in the human tissue contains vesicles, which are defined as matrix‐bound nanovesicles (MBVs). MBVs serve as one of the functional components in ECM, recapitulating part of the regulatory roles and in vivo microenvironment. In this study, extracellular vesicles from culture supernatants (SuEVs) and MBVs are isolated from the conditioned medium or ECM, respectively, of 3D human mesenchymal stem cells. Nanoparticle tracking analysis shows that MBVs are smaller than SuEVs (100–150 nm). Transmission electron microscopy captures the typical cup shape morphology for both SuEVs and MBVs. Western blot reveals that MBVs have low detection of some SuEV markers such as syntenin‐1. miRNA analysis of MBVs shows that 3D microenvironment enhances the expression of miRNAs such as miR‐19a and miR‐21. In vitro functional analysis shows that MBVs can facilitate human pluripotent stem cell‐derived forebrain organoid recovery after starvation and promote high passage fibroblast proliferation. In macrophage polarization, 2D MBVs tend to suppress the pro‐inflammatory cytokine IL‐12 β , while 3D MBVs tend to enhance the anti‐inflammatory cytokine IL‐10. This study has the significance in advancing the understanding of the bio‐interface of nanovesicles with human tissue and the design of cell‐free therapy for treating neurological disorders such as ischemic stroke.
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Integration of postmortem amygdala expression profiling, GWAS, and functional cell culture assays: neuroticism-associated synaptic vesicle glycoprotein 2A (SV2A) gene is regulated by miR-133a and miR-218
Recent genome-wide studies have begun to identify gene variants, expression profiles, and regulators associated with neuroticism, anxiety disorders, and depression. We conducted a set of experimental cell culture studies of gene regulation by micro RNAs (miRNAs), based on genome-wide transcriptome, proteome, and miRNA expression data from twenty
- NSF-PAR ID:
- 10186045
- Publisher / Repository:
- Nature Publishing Group
- Date Published:
- Journal Name:
- Translational Psychiatry
- Volume:
- 10
- Issue:
- 1
- ISSN:
- 2158-3188
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract In the tumor microenvironment, immune cells have emerged as key regulators of cancer progression. While much work has focused on characterizing tumor‐related immune cells through gene expression profiling, microRNAs (miRNAs) have also been reported to regulate immune cells in the tumor microenvironment. Using regression‐based computational methods, we have constructed for the first time, immune cell signatures based on miRNA expression from The Cancer Genome Atlas breast and ovarian cancer datasets. Combined with existing mRNA immune cell signatures, the integrated mRNA‐miRNA leukocyte signatures are better able to delineate prognostic immune cell subsets within both cancers compared to the mRNA or miRNA signatures alone. Moreover, using the miRNA signatures, the anti‐inflammatory M2 macrophages emerged as the most significantly prognostic cell type in the breast cancer data (HR [hazard ratio]: 12.9; CI [confidence interval]: 3.09‐52.9;
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