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Metabolic and transcriptional changes across osteogenic differentiation of mesenchymal stromal cells

ABSTRACT: Metabolic and transcriptional changes across osteogenic differentiation of mesenchymal stromal cells

PROVIDER: PRJNA789852 | ENA |

REPOSITORIES: ENA

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Metabolic and transcriptional changes across osteogenic differentiation of mesenchymal stromal cells

Project description:Mesenchymal stromal cells (MSCs) are multipotent post-natal stem cells with applications in tissue engineering and regenerative medicine. MSCs can differentiate into osteoblasts, chondrocytes, or adipocytes, with functional differences in cells during osteogenesis accompanied by metabolic changes. The temporal dynamics of these metabolic shifts have not yet been fully characterized and are suspected to be of importance for therapeutic applications, such as osteogenesis optimization. Here, our goal was to characterize the metabolic shifts that occur during osteogenesis. We longitudinally profiled five key extracellular metabolites (glucose, lactate, glutamine, glutamate, and ammonia) from MSCs from four donors to classify osteogenic differentiation into three metabolic stages, defined by changes in the uptake and secretion rates of the metabolites in cell culture media. We used a combination of untargeted metabolomic analysis, targeted analysis of 13C-glucose labelled intracellular data, and RNA-sequencing data to reconstruct the gene regulatory network and further characterize cellular metabolism. The metabolic stages identified in this proof-of-concept study provide a framework for more detailed investigations aimed at identifying biomarkers of osteogenic differentiation and small molecule interventions to optimize MSC differentiation for clinical applications.

2021-12-20 | GSE191136 | GEO

Identification of differentially-expressed piRNAs in early osteogenic and chondrogenic differentiation of human bone marrow-mesenchymal stromal cells (hMSCs)

Project description:The aim of this study was to identify non-coding RNA that were differentially expressed 7 days after induction of osteogenic or chondrogenic differentiation in human bone marrow-mesenchymal stromal cells (MSCs).

2020-02-18 | GSE135587 | GEO

Identification of differentially-expressed miRNAs in early osteogenic and chondrogenic differentiation of human bone marrow-mesenchymal stromal cells (hMSCs)

2020-02-18 | GSE135586 | GEO

Identification of differentially-expressed circular RNAs in early osteogenic and chondrogenic differentiation of human bone marrow-mesenchymal stromal cells (hMSCs)

2020-02-18 | GSE135883 | GEO

Diverse effects of cyclic AMP variants on osteogenic and adipogenic differentiation of human mesenchymal stromal cells

Project description:Osteogenic differentiation of human mesenchymal stromal cells (hMSCs) may potentially be used in cell-based bone tissue-engineering applications to enhance the bone-forming potential of these cells. Osteogenic differentiation and adipogenic differentiation are thought to be mutually exclusive, and although several signaling pathways and cues that induce osteogenic or adipogenic differentiation, respectively, have been identified, there is no general consensus on how to optimally differentiate hMSCs into the osteogenic lineage. Some pathways have also been reported to be involved in both adipogenic and osteogenic differentiation, as for example, the protein kinase A (PKA) pathway, and the aim of this study was to investigate the role of cAMP/PKA signaling in differentiation of hMSCs in more detail. We show that activation of this pathway with dibutyryl-cAMP results in enhanced alkaline phosphatase expression, whereas another cAMP analog induces adipogenesis in long-term mineralization cultures. Adipogenic differentiation, induced by 8-bromo-cAMP, was accompanied by stronger PKA activity and higher expression of cAMP-responsive genes, suggesting that stronger activation correlates with adipogenic differentiation. In addition, a whole-genome expression analysis showed an increase in expression of adipogenic genes in 8-br-cAMP-treated cells. Furthermore, by means of quantitative polymerase chain reaction, we show differences in peroxisome proliferator-activated receptor-gamma activation, either alone or in combination with dexamethasone, thus demonstrating differential effects of the PKA pathway, most likely depending on its mode of activation.

2018-08-05 | E-MTAB-7038 | biostudies-arrayexpress

Changes of miRNAs during osteogenic differentiation of PDGFRa+ mesenchymal progenitors derived from human skeletal muscle

Project description:Comprehensive analyses of miRNAs expression were performed using miRNA microarrays during osteogenic differentiation of PDGFRa+ mesenchymal progenitors isolated from human skeletal muscle to identify miRNAs that are involved in osteogenesis of PDGFRa+ mesenchymal progenitors. PDGFRa+ mesenchymal progenitors were isolated from the gluteus medius muscles of two different patients, and then subjected to osteogenic induction. Expression of miRNAs was examined using miRNA microarrays at the time points of one week and two weeks after osteogenic induction and were compared with that of uninduced cells.

2013-08-01 | E-GEOD-39361 | biostudies-arrayexpress

Metabolic and Transcriptional Changes across Osteogenic Differentiation of Mesenchymal Stromal Cells.

Project description: Not available

| S-EPMC8698318 | biostudies-literature

MicroRNA profiling of human umbilical cord mesenchymal stem cells during osteogenic differentiation

Project description:The time course experiment was designed as follow: (1) Mesenchymal stem cell (indifferentiated cells)/ time 0h; (2) After 24 h of osteogenic induction; (3) After 48 h of osteogenic induction (4) After 7 days of osteogenic induction.

2009-10-10 | E-MEXP-2259 | biostudies-arrayexpress

Changes of miRNAs during osteogenic differentiation of PDGFRa+ mesenchymal progenitors derived from human skeletal muscle

2013-08-01 | GSE39361 | GEO

Transcription profiling of human bone marrow mesenchymal stromal cells before and after stimulation with dexamethasone to study the early molecular processes of osteogenic differentiation

Project description:Human adult mesenchymal stromal cells (hMSC) have the potential to differentiate into chondrogenic, adipogenic or osteogenic lineages, providing a potential source for tissue regeneration. An important issue for efficient bone regeneration is to identify factors that can be targeted to promote the osteogenic potential of hMSCs. Using transcriptomic analysis, we found that integrin alpha5 (ITGA5) expression is upregulated during dexamethasone-induced hMSCs osteoblast differentiation. Gain-of-function studies showed that ITGA5 promotes the expression of osteoblast phenotypic markers as well as in vitro osteogenesis in hMSCs. Downregulation of endogenous ITGA5 using shRNA blunted osteoblast marker expression and osteogenic differentiation. Pharmacological and molecular analyses showed that the enhanced hMSCs osteoblast differentiation induced by ITGA5 was mediated by activation of FAK/ERK1/2-MAPKs and PI3K signaling pathways. Remarkably, activation of ITGA5 using a specific antibody that primes the integrin or a peptide that specifically activates ITGA5 was sufficient to enhance ERK1/2-MAPKs and PI3K signaling and to promote osteoblast differentiation and osteogenic capacity of hMSCs. We also demonstrate that hMSCs engineered to over-express ITGA5 exhibited a marked increase in their osteogenic potential in vivo. These findings not only reveal that ITGA5 is required for osteoblast differentiation of adult human MSCs but also provide a novel targeted strategy using ITGA5 agonists to promote the osteogenic capacity of hMSCs, which may be used for tissue regeneration in bone disorders where the recruitment or capacity of MSCs is compromised. Experiment Overall Design: Gene expression profiles were generated from bone marrow MSC before and 1, 3 and 7 days after stimulation with 10E-7M dexamethasone to study the early molecular processes of osteogenic differentiation. 3 replicates per timepoint.

2009-09-18 | E-GEOD-18043 | biostudies-arrayexpress

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