Mir-483 regulates the senescence of human adipose-derived mesenchymal stem cells through IGF1
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE138879 | GEO | 2020/09/21
REPOSITORIES: GEO
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Project description:Human adipose-derived mesenchymal stem cells (hADSCs) are an ideal source of seed cells for regenerative applications and tissue engineering. However, long-term in vitro culture of hADSCs reduces their quantity and quality, which lessens their value in research and clinical applications. The molecular mechanisms underlying this biological process are poorly defined. Recently identified microRNAs (miRNAs) have emerged as critical modulators of cellular senescence. In this study, we examined the changes in hADSCs undergoing senescence. Significant miR-483-3p upregulation was noted during in vitro passaging of hADSCs, which correlated with the adipogenic differentiation and cellular senescence. Knockdown of miR-483-3p retarded the adipogenic differentiation potential of hADSCs and reduced cellular senescence. Dual-luciferase reporter assays identified insulin-like growth factor-1 (IGF1) as the target gene of miR-483-3p. IGF1 inhibition confirmed its inhibitory effects on replicative senescence in hADSCs. In conclusion, our study revealed essential regulatory roles of miR-483-3p in the adipogenesis and aging of hADSCs mediated by targeting IGF1.
| S-EPMC7467354 | biostudies-literature
Project description:Mir-483 regulates the senescence of human adipose-derived mesenchymal stem cells through IGF1
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Project description:To further understand mechanisms governing adipogenic fate commitment, we perform a time course transcriptomic study of progenitors at 0, 3, 7 and 14 days post adipogenic induction. The progenitor cells undergo large scale gene expression changes within 3 days of exposure to adipogenic induction and adiponectin expression is strongly induced at day 3. The early detection of ADIPOQ expression suggests fate commitment occurs within 3 days of induction.
2023-04-01 | GSE198481 | GEO
Project description:Human mesenchymal stem cells (hMSC) have an extensive potential for clinical applications in cell therapy. However, very little is known of the specific molecular regulatory mechanisms that control the therapeutical properties of these cells. We aimed to identify microRNAs (miRNAs) that could be involved in controlling the transition between the self-renewing (undifferentiated) and the reparative (differentiated) phenotypes of hMSCs. MicroRNA microarrays were used to identify miRNAs that are upregulated in undifferentiated hMSCs. For that, we compared the miRNA expression profiles of undifferentiated bone marrow-derived hMSCs with the same primary cell lines after 9 days of in vitro adipogenic or osteogenic induction. We also compared the miRNA expression profiles of undifferentiated hMSCs with skin fibroblasts (a mesenchymal cell lineage with a more restricted differentiation potential). These experiments allowed us to identify miR-335 as the only miRNA downregulated upon MSC differentiation as well as in MSCs in comparison with skin fibroblasts. Gene expression microarrays were used to identify genes that are downregulated in hMSCs overexpressing miR-335. We compared the miRNA expression profiles of hMSCs transduced with a lentiviral vector encoding miR-335 with MSCs transduced with a control lentiviral vector. Our results suggest miR-335 downregulation could be one of the triggers for the initiation of MSCs activities involved in tissue repair and remodelling, including cell migration and differentiation. We compared the miRNA expression profiles of undifferentiated bone marrow-derived hMSCs with the same primary cell lines after 9 days of adipogenic or osteogenic induction, as well as with skin fibroblasts. A total of four independent samples were used for each condition. For the adipogenic/osteogenic vs. undifferentiated MSC comparison, the RNA samples were pooled (two independent samples/pool) before labeling. We also compared the miRNA expression profiles of hMSCs transduced with the lentiviral vector pLV-EmGFP-MIRN335 with MSCs transduced with the control vector pLV-EmGFP-Mock. For the gene expression microarrays, a total of three independent samples were used for each condition.
2010-05-06 | E-GEOD-19232 | biostudies-arrayexpress
Project description:To understand the specific transcriptomic changes in cells undergoing adipogenic differentiation, we performed single cell RNA-seq on two separate cultures: one corresponding to multipotent progenitors grown to confluency but not subjected to differentiation stimuli, and the second corresponding to progenitors exposed to adipogenic media for 3 days. Homogenous multipotent progenitors underwent two distinct fate trajectories rapidly upon induction of adipose differentiation, one toward the adipocyte fate, and the other towards a distinct, undifferentiated state.
2023-04-01 | GSE198482 | GEO
Project description:Background: Obesity is characterized as a disease that directly affects the whole-body metabolism and is associated with excess fat mass and several related comorbidities. Dynamics of the adipocyte hypertrophy and hyperplasia play an important role in health and disease, especially in obesity. Human adipose-derived stem cells (hASC) represent an important source for understanding the entire adipogenic differentiation process. However, little is known about the triggering step of adipogenesis in hASC. Here, we performed a proteogenomic approach for understanding the protein abundance alterations expression changes during the initiation of the adipogenic differentiation process. Methods: hASC were isolated from adipose tissue from three donors, characterized and expanded. Cells were cultured for 24 hours in adipogenic differentiation medium followed to protein extraction. We used shotgun proteomics to compare the proteomic profile of 24h-adipogenic differentiated and undifferentiated hASC. Besides, we used our previously next-generation sequencing data (RNA-seq) from the total and polysomal mRNA fractions of hASC to study post-transcriptional regulation during the initial steps of adipogenesis. Results: We identified a total of 3,.420 proteins out of and 48,.336 peptides, being 92 exclusively identified proteins in the undifferentiated hASC and 53 exclusive proteins in 24h-differentiated cells. Using a stringent criterion, we identified 33 differentially abundant proteins when compare 24h-differentiated versus undifferentiated hASC (14 upregulated and 19 downregulated, respectively). Among the upregulated proteins, we shortlist identified several adipogenic-related proteins. Combined analysis of the proteome and the transcriptome allowed the identification of positive correlation coefficients between proteins and mRNAs. Conclusions: These results demonstrate a specific proteome profile related to adipogenesis at the very beginning (24h) of the differentiation process in hASC, which represents an important piece for a better understanding of human adipogenesis and obesity. In addition, the adipogenic differentiation is fine-tuning regulated at transcriptional, post-transcriptional and post-translational levels.
2022-02-17 | PXD026299 | Pride
Project description:The human microRNA hsa-miR-29a is a member of the miR-29 family of microRNAs, which is expressed in the adipogenic lineage. To identify putative direct target mRNAs of the miR-29 family, and to get an idea about potential functions of the miR-29 family in adipocyte development, we transfected human Multipotent Adipose-Derived Stem (hMADS) cells with miR-29a mimics (leading to elevation of intracellular levels of mature miR-29a). Subsequently, gene expression profiling was performed for hMADS cells at day 0 (48 h after transfection) and at day 3, i.e. 3 days after adipocyte differentiation was induced by a chemically defined medium.
2019-01-23 | GSE65704 | GEO
Project description:human Multipotent Adipose-Derived Stem (hMADS) cells were subjected to adipogenic differentiation in vitro and microRNA expression was analyzed during differentiation. Total RNA was extracted at day 0 (AD0), day 3 (AD3) and day 8 (AD8) of differentiation, two biological replicates (1) and (2), and microRNA profiles were established with SOLiD sequencing.
2011-07-03 | E-GEOD-25715 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) can regulate cellular differentiation processes by modulating multiple pathways simultaneously. Previous studies to analyze in vivo miRNA expression patterns in developing human limb cartilage tissue identified significant downregulation of miR-483 in hypertrophic chondrocytes relative to proliferating and differentiated chondrocytes. To test the function of miR-483 during chondrogenesis, lentiviral strategies were used to overexpress miR-483 during in vitro chondrogenesis of human bone marrow-derived mesenchymal stem cells (hBM-MSCs). While the in vivo expression patterns led us to hypothesize that miR-483 may enhance chondrogenesis or suppress hypertrophic marker expression, surprisingly, miR-483 overexpression reduced chondrocyte gene expression and cartilage matrix production. In addition, cell death was induced at later stages of the chondrogenesis assay. Mechanistic studies revealed that miR-483 overexpression resulted in downregulation of the TGF-β pathway member SMAD4, a known direct target of miR-483-3p. From these studies, we conclude that constitutive overexpression of miR-483 in hBM-MSCs inhibits chondrogenesis of these cells and does not represent an effective strategy to attempt to enhance chondrocyte differentiation and anabolism in this system in vitro. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2369-2377, 2017.
| S-EPMC5573664 | biostudies-literature
Project description:Human mesenchymal stem cells (hMSC) have an extensive potential for clinical applications in cell therapy. However, very little is known of the specific molecular regulatory mechanisms that control the therapeutical properties of these cells. We aimed to identify microRNAs (miRNAs) that could be involved in controlling the transition between the self-renewing (undifferentiated) and the reparative (differentiated) phenotypes of hMSCs. MicroRNA microarrays were used to identify miRNAs that are upregulated in undifferentiated hMSCs. For that, we compared the miRNA expression profiles of undifferentiated bone marrow-derived hMSCs with the same primary cell lines after 9 days of in vitro adipogenic or osteogenic induction. We also compared the miRNA expression profiles of undifferentiated hMSCs with skin fibroblasts (a mesenchymal cell lineage with a more restricted differentiation potential). These experiments allowed us to identify miR-335 as the only miRNA downregulated upon MSC differentiation as well as in MSCs in comparison with skin fibroblasts. Gene expression microarrays were used to identify genes that are downregulated in hMSCs overexpressing miR-335. We compared the miRNA expression profiles of hMSCs transduced with a lentiviral vector encoding miR-335 with MSCs transduced with a control lentiviral vector. Our results suggest miR-335 downregulation could be a critical trigger for the initiation of MSCs activities involved in tissue repair and remodelling, including cell proliferation, migration and differentiation.
2010-03-01 | GSE19232 | GEO