Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1051599 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27186962_1.fastq.gz | Fastqsanger.gz | |||
| SRR27186962_2.fastq.gz | Fastqsanger.gz | |||
| SRR27186963_1.fastq.gz | Fastqsanger.gz | |||
| SRR27186963_2.fastq.gz | Fastqsanger.gz | |||
| SRR27186964_1.fastq.gz | Fastqsanger.gz |
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Project description:Biphasic Regulation of Epigenetic State by Matrix Stiffness during Cell Reprogramming
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Project description:In this study, we investigate how matrix stiffness regulates chromatin reorganization and cell reprogramming, and find that matrix stiffness acts as a biphasic regulator of epigenetic state and fibroblast-to-neuron conversion efficiency, maximized at an intermediate stiffness of 20 kPa. ATAC-sequencing analysis shows the same trend of chromatin accessibility to neuronal genes at these stiffness levels. Concurrently, we observe peak levels of histone acetylation and histone acetyltransferase (HAT) activity in the nucleus on matrices at 20 kPa, and inhibiting HAT activity abolishes matrix stiffness effects. G-actin and cofilin, the co-transporters shuttling HAT into the nucleus, rises with decreasing matrix stiffness; however, reduced importin-9 on soft matrices limits nuclear transport. These two factors result in a biphasic regulation of HAT transport into the nucleus, which is directly demonstrated on matrices with dynamically tunable stiffness. These findings unravel a mechanism of the mechano-epigenetic regulation that is valuable for cell engineering in disease modeling and regenerative medicine applications.
2023-12-19 | GSE250068 | GEO
Project description:In this study, we investigate how matrix stiffness regulates chromatin reorganization and cell reprogramming, and find that matrix stiffness acts as a biphasic regulator of epigenetic state and fibroblast-to-neuron conversion efficiency, maximized at an intermediate stiffness of 20 kPa. ATAC-sequencing analysis shows the same trend of chromatin accessibility to neuronal genes at these stiffness levels. Concurrently, we observe peak levels of histone acetylation and histone acetyltransferase (HAT) activity in the nucleus on matrices at 20 kPa, and inhibiting HAT activity abolishes matrix stiffness effects. G-actin and cofilin, the co-transporters shuttling HAT into the nucleus, rises with decreasing matrix stiffness; however, reduced importin-9 on soft matrices limits nuclear transport. These two factors result in a biphasic regulation of HAT transport into the nucleus, which is directly demonstrated on matrices with dynamically tunable stiffness. These findings unravel a mechanism of the mechano-epigenetic regulation that is valuable for cell engineering in disease modeling and regenerative medicine applications.
2023-12-19 | GSE250066 | GEO
Project description:The interplay between the extracellular matrix (ECM) and prostate cancer (PCa) tumor has been shown to increase ECM stiffness, correlating with more aggressive disease forms. However, the impact of ECM stiffness on the androgen receptor (AR), a primary PCa treatment target, remains elusive. Here, we aimed to explore whether matrix stiffness influences PCa progression, transcriptional regulation, chromatin state, and AR function in AR-positive PCa cells under varying ECM stiffness conditions. We utilized ATAC-seq and RNAseq in different ECM conditions and the SUC2 metastatic prostate adenocarcinoma patient dataset to understand the role of ECM stiffness on chromatin state, androgen response genes and to evaluate the effect of matrix stiffness on prostate cancer progression. Results showed that increased ECM stiffness elevated the expression of genes related to proliferation and differentiation. In contrast, androgen response genes were most induced in soft ECM conditions. Combining chromatin accessibility with transcriptomic results revealed that androgen response genes were more transcriptionally available in soft ECM conditions. Additionally, increased ECM stiffness upregulated genes associated with low overall survival in the SUC2 dataset. Taken together, our results indicate that high expression of hard matrix stiffness genes potentially promotes prostate cancer progression leading to more aggressive forms of the disease with poor survival rate.
2025-03-06 | GSE272028 | GEO
Project description:The interplay between the extracellular matrix (ECM) and prostate cancer (PCa) tumor has been shown to increase ECM stiffness, correlating with more aggressive disease forms. However, the impact of ECM stiffness on the androgen receptor (AR), a primary PCa treatment target, remains elusive. Here, we aimed to explore whether matrix stiffness influences PCa progression, transcriptional regulation, chromatin state, and AR function in AR-positive PCa cells under varying ECM stiffness conditions. We utilized ATAC-seq and RNAseq in different ECM conditions and the SUC2 metastatic prostate adenocarcinoma patient dataset to understand the role of ECM stiffness on chromatin state, androgen response genes and to evaluate the effect of matrix stiffness on prostate cancer progression. Results showed that increased ECM stiffness elevated the expression of genes related to proliferation and differentiation. In contrast, androgen response genes were most induced in soft ECM conditions. Combining chromatin accessibility with transcriptomic results revealed that androgen response genes were more transcriptionally available in soft ECM conditions. Additionally, increased ECM stiffness upregulated genes associated with low overall survival in the SUC2 dataset. Taken together, our results indicate that high expression of hard matrix stiffness genes potentially promotes prostate cancer progression leading to more aggressive forms of the disease with poor survival rate.
2025-03-06 | GSE272027 | GEO
Project description:Matrix stiffness modulates androgen response genes and chromatin state in prostate cancer (RNA-seq)
| PRJNA1134738 | ENA
Project description:BACKGROUND: Previous genomic studies with human tissues have compared differential gene expression between 2 conditions (ie, normal versus diseased) to identify altered gene expression in a binary manner; however, a potentially more informative approach is to correlate the levels of gene expression with quantitative physiological parameters. METHODS AND RESULTS: In this study, we have used this approach to examine genes whose expression correlates with arterial stiffness in human aortic specimens. Our data identify 2 distinct groups of genes, those associated with cell signaling and those associated with the mechanical regulation of vascular structure (cytoskeletal-cell membrane-extracellular matrix). Although previous studies have concentrated on the contribution of the latter group toward arterial stiffness, our data suggest that changes in expression of signaling molecules play an equally important role. Alterations in the profiles of signaling molecules could be involved in the regulation of cell cytoskeletal organization, cell-matrix interactions, or the contractile state of the cell. CONCLUSIONS: Although the influence of smooth muscle contraction/relaxation on arterial stiffness could be controversial, our provocative data would suggest that further studies on this subject are indicated.<br><br>Note that files GSM6179.txt and GSM6182.txt as imported from GEO are identical.
2007-12-13 | E-GEOD-420 | biostudies-arrayexpress
Project description:We tested the hypothesis that increasing matrix stiffness on which normal human lung fibroblasts are grown promotes the expression of a fibrogenic cellular transcriptomic program. Keywords: Human lung fibroblast, matrix stiffness, PTGS2, COX-2, Prostaglandin E2 Total RNA extracted from normal human lung fibroblasts from 3 human subjects and separately grown on 5 discrete matrix stiffness conditions: 100, 400, 1600, 6400, 25600 Pascals.
2010-07-15 | E-GEOD-22011 | biostudies-arrayexpress
Project description:In vitro cultures of primary cardiac fibroblasts (CFs), the major extracellular matrix (ECM)-producing cells of the heart, are used to determine molecular mechanisms of cardiac fibrosis. However, the supraphysiologic stiffness of tissue culture polystyrene (TCPS) automatically triggers the conversion of CFs into an activated myofibroblast-like state, and serial passage of the cells results in the induction of replicative senescence. These dramatic phenotypic switches confound interpretation of experimental data obtained with cultured CFs. In an attempt to circumvent TCPS-induced activation and senescence of CFs, we utilized poly (ethylene glycol) (PEG) hydrogels as cell culture platforms with low and high stiffness formulations to mimic healthy and fibrotic cardiac ECM, respectively. As hypothesized, low hydrogel stiffness converted activated CFs into a quiescent state with reduced abundance of a-smooth muscle actin (a-SMA)-containing stress fibers. Unexpectedly, lower substrate stiffness concomitantly augmented CF senescence, marked by elevated senescence-associated b-galactosidase (SA-b-Gal) activity and increased expression of p16 and p21, which are cyclin-dependent kinase (CDK) inhibitors and markers of senescence. Using dynamically stiffening hydrogels with phototunable crosslinking capabilities, we demonstrate that substrate-induced CF senescence is partially reversible. RNA-sequencing analysis revealed widespread transcriptional reprogramming of CFs cultured on low stiffness hydrogels, with a dramatic reduction in the expression of profibrotic genes encoding ECM proteins, and an attendant increase in expression of NF-kB-responsive inflammatory genes that typify the senescence-associated secretory phenotype (SASP). Our findings further demonstrate that alterations in matrix stiffness profoundly impact CF cell state transitions, and suggest mechanisms by which CFs change phenotype in vivo depending on the stiffness of the myocardial microenvironment to which they are exposed.
2023-10-24 | GSE244614 | GEO