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Gene expression data from diabetic human adipose-derived stem cells (d-hASC) treated with 1uM oleacein

ABSTRACT: Gene expression profiling reveals multiple biological functions of oleacein in diabetic model. We evaluated the effects of oleacein on diabetic human adipose-derived stem cells. We performed an untargeted whole-genome transcriptome analysis to explore functionality of oleacein in a diabetic adipose stem cell-based tool.

ORGANISM(S): Homo sapiens

PROVIDER: GSE230618 | GEO | 2023/07/19

REPOSITORIES: GEO

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Project description:Pericytes (PCs) are multipotent contractile cells that wrap around the endothelial cells to maintain the blood vessel's functionality and integrity. The hyperglycemia associated with Type 2 diabetes mellitus (T2DM) was shown to impair the function of PCs and increase the risk of diabetes complications. In this study, we aimed to investigate the deleterious effect of the diabetic microenvironment on the regenerative capacities of human PCs. PCs isolated from human adipose tissue were cultured in the presence or absence of serum collected from diabetic patients (DS). The functionality of PCs was analysed after 6, 14, and 30 days. Microscopic examination of PCs cultured in DS (DS-PCs) showed increased aggregate formation and altered surface topography with hyperbolic invaginations. Compared to PCs cultured in normal serum (NS-PCs), DS-PCs showed more fragmented mitochondria and thicker nuclear membrane. DS caused impaired angiogenic differentiation of PCs as confirmed by tube formation, decreased VEGF-A and IGF-1 gene expression, upregulated TSP1, PF4, actin related protein 2/3 complex and downregulated COL21A1 protein expression. These cells suffered higher apoptotis and showed higher expression of Clic4, apoptosis facilitator BCl-2-like protein serine/threonine protein phosphatase, and Caspase-7 proteins. DS-PCs showed dysregulated DNA repair genes CDKN1A, SIRT1, XRCC5 and TERF2 and up-regulation of the pro-inflammatory genes ICAM1, IL-6, and TNF-α. DS treated cells also showed disruption in the expression of the focal adhesion and binding proeins TSP1, TGF- β, fibronectin and PCDH7. DS-PCs showed resistance mechanisms upon exposure to diabetic microenvironment by maitining the intracellular ROS level and upregulation of ECM organizing proteins vinculin, IQGAP1, and tubulin beta chain.These data show that the diabetic microenvironment exert a deleterious effect on the regenerative capacities of human adipose tissue-derived PCs, and may thus have possible implications on the vascular complications of type-2 diabetes mellitus. Nevertheless, their protective mechanisms when initially exposed to DS could provide a promising cellular therapy for T2DM.

Project description:Purpose: Whole-transcriptome sequencing technology and bioinformatics analysis were applied to systematically analyze the differentially expressed mRNAs, lncRNAs, circRNAs and miRNAs in adipose stem cells (ASCs) from diabetic, old and young patients. Methods: MRNAs, lncRNAs and cirRNAs profiles of adipose stem cells were generated by RNA sequencing, in triplicate, using Illumina HiSeq X Ten . MiRNAs profiles of adipose stem cells were generated by RNA sequencing, in triplicate, using BGISEQ-500. The sequence reads that passed quality filters were analyzed at the transcript isoform level by using sequence analysis programs, including HISAT, Stringtie, CIRI, find_circ and DESeq. qRT–PCR validation was performed using Takara, Vazyme and Clontech kits. Results: The data showed that 1377 mRNAs, 5353 circRNAs, 932 lncRNAs and 85 miRNAs were significantly differently expressed in adipose stem cells from old patients compared with young patients, with a fold change ≥2 or ≤ -2 and q value <0.001. The data showed that 1878 mRNAs, 22988 circRNAs, 2638 lncRNAs and 122 miRNAs were significantly differently expressed (DE) in adipose stem cells from old patients compared with diabetic patients, with a fold change ≥2 or ≤ -2 and q value <0.001. The results of qRT-PCR confirmed 25 mRNAs, 9 lncRNAs, 8 circRNAs and 13 miRNAs which were consistent with the RNA-seq data. GO and KEGG analyses demonstrated DE mRNAs were significantly enriched in aging and cell senescence terms separately. Conclusion: Our group simultaneously examined the changing expression of miRNAs, mRNAs, lncRNAs and circRNAs in ASCs associated with diabetes and aging. GO and KEGG pathway analyses were conducted to annotate the possible function of the differentially expressed mRNAs. PPI networks were established in order to find critical protein genes highly involved in our disease models. The ceRNA networks including lncRNA-miRNA-mRNA and cirRNA-miRNA-mRNA interactions were successfully constructed based on the bioinformatic analyses and PCR results. Thus, this study may contribute to our understanding of the underlying mechanisms of ASCs instability and provide novel targets to reverse the dysfunction of ASCs isolated from diabetic and old patients.

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Gene expression data from diabetic human adipose-derived stem cells (d-hASC) treated with 1uM oleacein

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