Mechanical control of MSC adipogenesis does not require Lamin A/C
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA659991 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12540031_1.fastq.gz | Fastqsanger.gz | |||
| SRR12540031_2.fastq.gz | Fastqsanger.gz | |||
| SRR12540032_1.fastq.gz | Fastqsanger.gz | |||
| SRR12540032_2.fastq.gz | Fastqsanger.gz | |||
| SRR12540033_1.fastq.gz | Fastqsanger.gz |
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Project description:Mesenchymal stem cells (MSC) maintain the musculoskeletal system by differentiating into multiple cell types including osteocytes and adipocytes. Mechanical signals, including strain and low intensity vibration (LIV), are important regulators of MSC differentiation. Lamin A/C is a vital nucleoskeleton protein that provides mechanical properties to the nucleus and mechanical competency to MSCs. Loss of Lamin A/C has been associated with reduced structural integrity and genomic regulation of the nucleus, but direct involvement of Lamin A/C in mechanical regulation of MSC differentiation is unknown. We investigated the effects of Lamin A/C depletion on the nucleus and regulation of adipogenesis during mechanical stimulation. Upon Lamin A/C depletion, the nucleus experienced decreased area, height, volume, and stiffness while the focal adhesion phosphorylation in response to LIV and dynamic substrate strain remained intact. Cells experiencing Lamin A/C depletion undergo slower adipogenesis than control cells indicating a loss of genomic regulation due to the depletion of Lamin A/C. Mechanical stimulation via daily LIV application induced a reduction of adiponectin protein levels in both control and Lamin A/C depleted cells. RNA-seq data indicated a large adipogenic mRNA shift in control cells while Lamin A/C depleted cells showed a blunted adipogenic mRNA profile. Treatment with LIV did not induce large trascriptome changes in ether control or Lamin A/C depleted MSCs except for lowered intereferon response, suggested that LIV effects on adipogenesis may not occur at the transcriptional level. In summary, focal adhesion activation by dynamic mechanical signals and LINC complex elements largely remain unaltered under Lamin A/C depletion. While the adipogenic commitment was dependent upon Lamin A/C, the reduction of adiponectin protein in response to LIV was independent of Lamin A/C indicating that the Lamin A/C depletion and mechanical regulation of adipogenesis may not utilize similar pathways to elicit a response in MSCs.
2020-11-15 | GSE157056 | GEO
Project description:Mesenchymal stem cells (MSC) have emerged as potent therapeutic tool for a number of pathologies, including immune ones. However, unwelcome effects of MSC on the blood coagulation were revealed in some cases, which require more in-depth analysis. In this study, we explored the trombotic properties of human MSC from umbilical cord. We revealed strong procoagulant effects of umbilical cord MSC toward human and rat whole blood and platelets-free plasma using rotational thromboelastometry and thrombodynamics tests. The similar potentiation of clotting was demonstrated for MSC-derived extracellular vesicles (EV). In order to suggest approaches to avoid unwanted effects we studied the impact of heparin supplement on MSC/EV procoagulation properties. We found that therapeutic doses of unfractionated heparin injected in the patient's blood (administered in vivo) did not abrogate the procoagulant properties of MSC. Mass-spectrometry analysis of proteins of MSC and EV involved in coagulation-associated pathways was used to evaluate mechanisms of protrombotic effects.
2019-03-26 | PXD012768 | Pride
Project description:Mesenchymal stem cells (MSCs) maintain the musculoskeletal system by differentiating into multiple lineages, including osteoblasts and adipocytes. Mechanical signals, including strain and low-intensity vibration (LIV), are important regulators of MSC differentiation via control exerted through the cell structure. Lamin A/C is a protein vital to the nuclear architecture that supports chromatin organization and differentiation and contributes to the mechanical integrity of the nucleus. We investigated whether lamin A/C and mechanoresponsiveness are functionally coupled during adipogenesis in MSCs. siRNA depletion of lamin A/C increased the nuclear area, height, and volume and decreased the circularity and stiffness. Lamin A/C depletion significantly decreased markers of adipogenesis (adiponectin, cellular lipid content) as did LIV treatment despite depletion of lamin A/C. Phosphorylation of focal adhesions in response to mechanical challenge was also preserved during loss of lamin A/C. RNA-seq showed no major adipogenic transcriptome changes resulting from LIV treatment, suggesting that LIV regulation of adipogenesis may not occur at the transcriptional level. We observed that during both lamin A/C depletion and LIV, interferon signaling was downregulated, suggesting potentially shared regulatory mechanism elements that could regulate protein translation. We conclude that the mechanoregulation of adipogenesis and the mechanical activation of focal adhesions function independently from those of lamin A/C.
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Project description:To investigate the collective role of zinc finger proteins in adipogenesis, we induced adipogenesis using human mesenchymal stem cells (MSC) and compared the gene expression profiles using human Illumina beads arrays. We performed three independent experiments of time-series analysis (0h, 1h, 12h, 24h, 2d, 4d, 6d, 9d, 12d, 15d after induction of adipogenesis) in order to comprehensively capture the dynamic profiles of transcriptome during differentiation. Statistical filtering based on Analysis of Variance (ANOVA; p-value < 0.001, FDR 5%) and Gene Ontology classification using the Human Gene Nomenclature Database (HGNC) identified 618 out of 678 zinc finger proteins (ZFPs) that were significantly expressed during adipogenesis. Moreover, 34 out of 618 genes were differentially expressed more than 2-fold up or down regulated. The K-means clustering analysis further revealed four dynamic expression patterns: one gene in early-response, seven genes in transient, twenty genes in progressively-induced and four genes in the down-regulated, demonstrating the dynamic involvement of ZFPs in the process of adipocyte differentiation and maturation. Total RNA obteind from 10 different time points (0h, 1h, 12h, 24h, 2d, 4d, 6d, 9d, 12d, 15d) during adipogenesis from human Mesenchymal stem cell (MSC) to Adipocyte (ADP). Adipogensis was induced by the different cocktail of chemical compunds containing human-insulin, dexamethasone, indomethacin and IBMX.
2012-12-01 | E-GEOD-37836 | biostudies-arrayexpress
Project description:Dynamic interactions of nuclear lamins with chromatin through so-called lamin-associated domains (LADs) contribute to spatial arrangements of the genome. Here, we provide evidence for pre-patterning of differentiation-driven formation of lamin A/C LADs by domains of histone H2B modified by the nutrient sensor O-linked N-acetylglucosamine (H2BGlcNAc), which we term GADs. We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving (i) a spreading of lamin A/C-chromatin interactions during the transition from progenitor cell proliferation to cell cycle arrest, and (ii) a genome-scale redistribution these interactions through a process of LAD ‘exchange’ within hours of adipogenic induction. Chromatin state modeling reveals that lamin A/C LADs can be found both in active and repressive chromatin contexts which can be influenced by cell differentiation status. De novo formation of adipogenic lamin A/C LADs occurs non-randomly on GADs, consisting of megabase-size intergenic and repressive chromatin domains. Accordingly, while pre-differentiation lamin A/C LADs are gene-rich, post-differentiation LADs harbor repressive features reminiscent of lamin B1 LADs. Moreover, release of lamin A/C from genes directly involved in glycolysis concurs with their transcriptional upregulation after adipogenic induction, and with concordant downstream elevations in H2BGlcNAc levels and O-GlcNAc cycling. Our results unveil an epigenetic pre-patterning of adipogenic LADs by GADs, suggesting a coupling of developmentally regulated lamin A/C-genome interactions to a metabolically sensitive chromatin modification. Examination of LMNA and H2BGlcNAc binding in ASCs across differentiation
2015-09-04 | E-GEOD-63346 | biostudies-arrayexpress
Project description:Long-term dynamic compression enhanced the mechanical properties of MSC-seeded constructs only when loading was initiated after 21 days of chondrogenic differentiation. This study examined the molecular differences of chondrogenic MSCs compared to undifferentiated MSCs (TGF-beta vs no TGF-beta) and the effects of dynamic loading on MSC chondrogenesis (loading vs free-swelling). Free-swelling MSC-seeded constructs were cultured for 21 days in chemically defined media. Chondrogenesis was induced with TGF-beta3. Undifferentiated controls were maintained in parallel. After 21 days of chondrogenic differentiation, a subset of constructs were subjected to 21 days of dynamic compressive loading. On days 21 and 42, construct mechanical properties and biochemical content were assessed. Microarray analysis was carried out on day 3, day 21 and day 42 constructs. 6 arrays.
2010-11-01 | E-GEOD-18879 | biostudies-arrayexpress
Project description:Long-term dynamic compression enhanced the mechanical properties of MSC-seeded constructs only when loading was initiated after 21 days of chondrogenic differentiation. This study examined the molecular differences of chondrogenic MSCs compared to undifferentiated MSCs (TGF-beta vs no TGF-beta) and the effects of dynamic loading on MSC chondrogenesis (loading vs free-swelling).
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Project description:influence of lamin B rereceptor knockout and lamin A/C knockout on gene expression in cultured myoblast cells and in striated muscle tissue knockout samples are obtained by mating of heterozygous animals. Homozygous KO and wt animals of one litter are compared. Two boilogical replicates of KO samples are processed in parallel. wt samples are used as controls. One wt sample is processed per KO litter. Where appropriate two wt samples are used as biological replicates.
2013-01-28 | E-GEOD-37076 | biostudies-arrayexpress
Project description:Human umbilical cord matrix-mesenchymal stromal cells (hUCM-MSC) have demonstrated beneficial effects in experimental acute myocardial infarction (AMI). In this study, we investigated the outcome of the delivery of hUCM-MSC after reperfusion in a translational model of AMI in swine. We have found that intracoronary injection of the cell product was associated with improved systolic function and that improvement in mechanical performance. This did not depend on the reduction of morphological infarct size alone, despite treated animals showing signs of less adverse remodeling.
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Project description:influence of lamin B rereceptor knockout and lamin A/C knockout on gene expression in cultured myoblast cells and in striated muscle tissue
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