RNA-seq of human adipose-derived stromal/stem cells with significant differences in osteogenic differentiation
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE220162 | GEO | 2024/12/28
REPOSITORIES: GEO
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Project description:Naringenin (NAR) is a prominent flavanone, and it has been recognized for its capacity to promote osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) in prior research. The present study aimed to explore how NAR promotes the osteogenic differentiation of hPDLSCs and to assess its efficacy in repairing alveolar bone defects. In the present study, the protein-protein interaction (PPI) network of NAR action was established by mRNA sequencing and network pharmacological analysis. Gene and protein expression were evaluated by PCR and western blotting. Alizarin red and alkaline phosphatase staining were employed to observe the osteogenic capacity of hPDLSCs, and immunofluorescence was used to examine the co-localization of NAR molecular probes and AKT in cells. Repair of mandibular defects was assessed by micro computed tomography (micro-CT), Masson staining and immunofluorescence. Additionally, computer simulation docking software was utilized to determine the binding affinity of NAR to the target protein AKT. The results demonstrated that activation of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) signaling pathway promoted the osteogenic differentiation of hPDLSCs. Inhibition of AKT, endothelial nitric oxide synthase and soluble guanylate cyclase individually attenuated NAR’s ability to promote the osteogenic differentiation of hPDLSCs. Micro-CT and Masson staining revealed more new bone formation at the defect site in the NAR gavage group. Immunofluorescence assays confirmed upregulated expression of Runt-related transcription factor 2 and osteopontin in the NAR gavage group. In conclusion, the present study suggests that NAR promotes the osteogenic differentiation of hPDLSCs by activating the NO-cGMP-PKG signaling pathway through its binding to AKT.
2024-05-23 | GSE266150 | GEO
Project description:SGLT-2 inhibitors, such as empagliflozin, have been shown to reduce the occurrence of cardiovascular events and delay the progression of atherosclerosis. However, its role in atherosclerotic calcification remains unclear. In this research, ApoE-/- mice were fed with western diet and empagliflozin was added to the drinking water for 24 weeks. Empagliflozin treatment significantly alleviated arterial calcification assessed by alizarin red and von kossa staining in aortic roots and reduced the lipid levels, while had little effect on body weight and blood glucose levels in ApoE-/- mice. In vitro studies, empagliflozin significantly inhibits calcification of primary vascular smooth muscle cells (VSMCs) and aortic rings induced by osteogenic media (OM) or inorganic phosphorus (Pi). RNA sequencing of VSMCs cultured in OM with or without empagliflozin showed that empagliflozin negatively regulated the osteogenic differentiation of VSMCs. And further studies confirmed that empagliflozin significantly inhibited osteogenic differentiation of VSMCs via qRT-PCR. Our study demonstrates that empagliflozin alleviates atherosclerotic calcification by inhibiting osteogenic differentiation of VSMCs, which addressed a critical need for the discovery of a drug-based therapeutic approach in the treatment of atherosclerotic calcification.
2023-11-22 | GSE243752 | GEO
Project description:In the current study, we have performed a gene expression analysis of well characterized and defined populations of human adipose-derived stem cells (hASCs) before and after in vitro induction of osteogenic and myogenic differentiation that allows identifying DNA methylation- regulated differentiation genes. We have also address the extent of the epigenetic programming of hASCs- derived differentiated cells by comparing the expression profiling of these cells with their somatic counterparts from primary tissues. Finally, we also compared the patterns of expression of hASCs (and their derivatives) Identify all genes or probe-sets whose expression was significantly different between control hASCs and each one of the two differentiated cell types (DIF.M and DIF.O),
2013-10-03 | E-GEOD-37329 | biostudies-arrayexpress
Project description:The treatment of bone defects caused by infection, trauma or neoplasms remains a clinical challenge. Autologous bone transplantation is limited by availability, donor site morbidity and surgical risk factors. This has given rise to stromal/stem-cell based therapy. Bone marrow derived stromal cells (BMSCs) have been studied to a large extent and show high regenerative potential but their use is limited by availability, donor site morbidity and the relatively low cell yield as they represent only <0.1% of cell harvested from bone marrow aspirate. At the same time, they are the closest mesenchymal stromal cells for bone tissue engineering given their tissue origin and, unlike other mesenchymal stromal cells, can support the formation of hematopoietic marrow. Adipose tissue derived stromal cells (ASCs) as part of the stromal vascular fraction of adipose tissue can as well undergo osteogenic differentiation but can be additionally isolated in a sufficient quantity from lipoaspirate after liposuction of abundant subcutaneous fat tissue. Here, it has been shown that there are no major differences in regard to proliferation or differentiation capacity of ASCs derived from subcutaneous fat of different anatomical regions. It has been shown that BMSCs are more prone to senescence during expansion and passage than ASCs and that ageing impacts proliferative capabilities of BMSCs more than that of ASCs while it has also been reported that osteogenic differentiation capacity is least impacted by age. Multiple studies have compared the characteristics of these two mesenchymal stromal cells in regard to bone tissue engineering in vitro. Most studies point to inferior extracellular matrix mineralization and lower expression of key osteogenic transcription markers like Runx2 in osteogenic differentiated ASCs compared to BMSCs. On the other hand, a study by Rath et al. found contrary results using particular culturing conditions like 3D bioglass scaffolds. An intraindividual comparison of human MSCs of three donors cultured on decellularized porcine bone confirmed superior osteogenic capacity of BMSCs compared to ASCs. In contrast to BMSCs, ASCs were not able to induce heterogenic ossification in a mouse model. In a sheep tibia defect model application of BMSCs resulted in a significantly higher amount of newly formed bone tissue. Importantly, Osteogenic differentiated ASCs do not support the formation of a hematopoietic marrow. Proteomics enables large-scale analysis of proteins present in a cell type and can be used to identify differentially regulated key proteins in a comparative approach. A comparative proteomic analysis of BMSCs and ASCs by Roche et al. in 2009 identified 556 proteins with 78% of these not being differentially regulated between these two cell populations, regarded as high similarity. Another comparative proteomic study of 2016 by Jeon et al. found 90 differentially regulated proteins out of 3000 total identified proteins. Both studies do not specify a number of different tissue donors and in part using cell lines. Looking for differences upon osteogenic differentiation, transcriptomic comparison of osteogenic differentiated porcine ASCs and BMSCs has been performed, resulting in 21 differentially expressed genes after 21 days of osteogenic culture conditions. Still, it remains unanswered, which are the key distinctive features of osteogenic differentiated ASCs and BMSCs at protein level that might help address the abovementioned weaknesses of ASCs in bone tissue engineering/regeneration for translational research. To overcome this need, an intraindividual comparative DIA based proteomic analysis of osteogenic differentiated human BMSC and ASCs was performed in this study.
2021-06-09 | PXD015223 | Pride
Project description:In the current study, we have performed a gene expression analysis of well characterized and defined populations of human adipose-derived stem cells (hASCs) before and after in vitro induction of osteogenic and myogenic differentiation that allows identifying DNA methylation- regulated differentiation genes. We have also address the extent of the epigenetic programming of hASCs- derived differentiated cells by comparing the expression profiling of these cells with their somatic counterparts from primary tissues. Finally, we also compared the patterns of expression of hASCs (and their derivatives)
2013-10-03 | GSE37329 | GEO
Project description:To investigate expression profile and potential role of lncRNAs in osteogenic differentiation of human adipose-derived stem cells (ASCs), whole genome lncRNA microarray was employed to identify lncRNAs that differentially expressed during osteogenesis of ASCs. Four individual human ASCs derived from four different donors were induced to differentiate into osteoblast in vitro. Expression profiles of lncRNAs and mRNAs of undifferentiated and osteogenic differentiated ASCs were obtained by microarray and compared. The genes that meet both fold change ≥2.0 and p<0.05 were considered as differentially expressed genes during osteogenic differentiation of human ASCs. Expression of five upregulated lncRNAs (SAA3P, LOC284080, XLOC_001453, XLOC_011980, HHIP-AS1) and five downregulated lncRNAs (XLOC_007489, CTC-564N23.3, XLOC_010397, XLOC_002619, LINC00638) from the microarray were quantified in the same RNA samples by real-time PCR, validating the microarray data.
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Project description:In the current study, we have performed a high-throughput CpG methylation analysis of well characterized and defined populations of human adipose-derived stem cells (hASCs) before and after in vitro induction of osteogenic and myogenic differentiation that allows identifying DNA methylation- regulated differentiation genes. We have also address the extent of the epigenetic programming of hASCs- derived differentiated cells by comparing the methylation profiling of these cells with their somatic counterparts from primary tissues. Finally, we also compared the patterns of CpG methylation of hASCs (and their derivatives) with the methylation profiles of myosarcoma and osteosrcoma cell lines. All the CpG methylation studies have been performed with the Infinium 27K methylation arrays (from Illumina).
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Project description:Background & Aims: Obesity is a complex disease that causes visceral WAT dysfunction and is associated with cardiovascular, chronic inflammatory and other metabolic pathologies.Adipose-derived stem cells (ASCs) are the key cells for adipose tissue homeostasis.However, how obesity may affect the biological functions of hASCs is not clear. We then performed gene expression profiling analysis using data obtained from RNA-seq of 8 different donors obese group,and 3 different donors lean group
2023-09-24 | GSE203371 | GEO
Project description:We have previously reported that the deficiency of p53 alone or in combination with Rb (Rb-/- p53-/-) in adipose-derived MSCs (ASCs) promotes leiomyosarcoma-like tumors in vivo. Here, we hypothesized that the source of MSCs and/or the cell differentiation stage could determine the phenotype of sarcoma development. To investigate whether there is a link between the source of MSCs and sarcoma phenotype, we generated p53-/- and Rb-/-p53-/- MSCs from bone marrow (BM-MSCs). Both genotypes of BM-MSCs initiated leiomyosarcoma formation similar to p53-/- and Rb-/-p53-/- ASCs. In addition, gene expression profiling revealed a link between p53- or Rb-p53-deficient BM-MSCs and ASCs and muscle-associated sarcomagenesis. These data suggest that the tissue source of MSC does not seem a crucial factor in the development of a particular sarcoma phenotype. To analyze whether the differentiation stage defines the sarcoma phenotype, BM-MSCs and ASCs were induced to differentiate towards the osteogenic lineage, and both p53 and Rb were excised using Cre-expressing adenovectors at different stages along osteogenic differentiation. Regardless of the level of osteogenic commitment, the inactivation of Rb and p53 in BM-MSC-derived, but not in ASC-derived, osteogenic progenitors gave rise to osteosarcoma-like tumors which could be serially transplanted. This indicates that the osteogenic differentiation stage of BM-MSCs imposes the phenotype of in vivo sarcoma development, and that BM-MSC-derived osteogenic progenitors rather than undifferentiated BM-MSCs, undifferentiated ASCs or ASC-derived osteogenic progenitors, represent the cell of origin for osteosarcoma development. To analyse whether the BM-MSC and Fat-MSC (ASC) differentiation stage may define the sarcoma phenotype, RbloxP/loxPp53loxP/loxP BM-MSCs and ASCs were induced to differentiate towards the osteogenic lineage and both Rb and p53 were excised with adenoviral vectors expressing the Cre-recombinase gene (Ad-CMV-Cre) at different stages (day 0 and 10) along osteogenic differentiation. NSG mice were inoculated subcutaneously with 5M-CM-^W10^6 mutant cells. Animals were killed when tumors reached 1 cm3 or 150 days after infusion. Some of the obtained tumors were mechanically disaggregated to establish ex vivo MSC-transformed cell lines. Gene expression analysis was performed using: WT BM-MSCs and ASCs, Rb-/-p53-/- BM-MSCs and ASCs previously differentiated to the osteogenic lineage for 10 days and a tumor cell line derived from p53-/-Rb-/- BM-MSC differentiated to the osteogenic lineage for 10 days.
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Project description:Human adipose-derived stem cells (hASCs) are a highly attractive source in bone tissue engineering.We found that MIR31HG significantly promote the osteogenic differentiation of hASCs. However, the underlying mechanisms still await investigations. Thus the alteration of gene expression induced by MIR31HG knockdown was investigated. We used microarrays to detail the global programme of gene expression when MIR31HG was knocked down in hASCs and identified distinct classes of dn-regulated genes during this process.
2018-10-07 | GSE73919 | GEO