Dataset Information

The extracellular matrix influences the miRNA landscape of human mesenchymal stromal/stem cells

ABSTRACT: Mesenchymal stromal/stem cells (MSCs) are promising therapeutic tools secreting a broad repertoire of pleiotropic molecules that promote tissue repair and regeneration. Recent advances in cell sheet technique demonstrate powerful improvement of MSCs regenerative capacity within the sheet retaining appropriate microenvironmental cues and suggest the instructing role of extracellular matrix (ECM). We found previously that the secretome of MSCs cultured on decellularized MSCs-derived ECM (dECM) is significantly enriched with dozen of cytokines, chemokines and growth factors in comparison to the secretome of MSCs cultured on routine plastic dishes. Enriched secretome was shown to have improved chemotactic and angiogenic properties, to stimulate C2C12 myoblast proliferation and promote skeletal muscle regeneration in murine in vivo model (Ushakov et al., 2024; Ushakov, Burova, 2024). Here we report novel findings about dECM-induced changes in miRNAs profile, another regulatory component of MSCs secretome. We performed miRNA-seq and found 17 differentially expressed miRNAs in endometrial MSCs (MESCs) with miR-146a-5p most upregulated. We also checked it’s expression in MSCs of various origin exposed to dECM and found miR-146a-5p upregulation to be correlated with general dECM-induced paracrine response. Besides, we found that miR-146a-5p mimic transfected to C2C12 myoblasts promote their proliferation suggesting miR-146a-5p contribution to myotropic effects of enriched secretome. These results provide new insights into how ECM as the component of MSCs niche influences secretory phenotype and modulate MSCs therapeutic properties.

ORGANISM(S): Homo sapiens

PROVIDER: GSE301921 | GEO | 2025/11/14

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Hepatitis C virus (HCV)-induced chronic liver disease is one of the leading causes of hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying HCC development following chronic HCV infection remain poorly understood. MicroRNAs (miRNAs) play an important role in cellular homeostasis within the liver and deregulation of the miRNome has been associated with liver disease including HCC. While host miRNAs are essential for HCV replication, viral infection in turn appears to induce alterations of intrahepatic miRNA networks. Although the cross-talk between HCV and liver cell miRNAs most likely contributes to liver disease pathogenesis, the functional involvement of miRNAs in HCV-driven hepatocyte injury and HCC remains elusive. Here, we combined a hepatocyte-like based model system, high-throughput small RNA-sequencing, computational analysis and functional studies to investigate HCV-miRNA interactions that may contribute to liver disease and HCC. Profiling analyses indicated that HCV infection differentially regulated the expression of 72 miRNAs by at least two-fold including miRNAs that were previously described to target genes associated with inflammation, fibrosis and cancer development. Further investigation demonstrated that miR-146a-5p was consistently increased in HCV-infected hepatocyte-like cells and primary human hepatocytes as well as in liver tissues from HCV-infected patients. Genome-wide microarray and computational analyses indicated that miR-146a-5p over-expression is related to liver disease and HCC development. Furthermore, we showed that miR-146a-5p positively impacts on late steps of the viral replication cycle thereby increasing HCV infection. Collectively, our data indicate that the HCV-induced increase in miR-146a-5p expression both promotes viral infection and is relevant for pathogenesis of liver disease. To explore the functional relevance of miR-146a-5p up-regulation, we performed a genome-wide transcriptomic analysis of hepatocyte-like cells upon ectopic miR-146a-5p expression.

Dataset Information

The extracellular matrix influences the miRNA landscape of human mesenchymal stromal/stem cells

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets