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Biphasic Regulation of Epigenetic State by Matrix Stiffness during Cell Reprogramming

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE250069 | GEO | 2023/12/19

REPOSITORIES: GEO

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Biphasic regulation of epigenetic state by matrix stiffness during cell reprogramming.

Project description: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 20 kPa matrices, and inhibiting HAT activity abolishes matrix stiffness effects. G-actin and cofilin, the cotransporters 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 nucleus, which is directly demonstrated on matrices with dynamically tunable stiffness. Our findings unravel a mechanism of the mechano-epigenetic regulation that is valuable for cell engineering in disease modeling and regenerative medicine applications.

| S-EPMC10866547 | biostudies-literature

Biphasic Regulation of Epigenetic State by Matrix Stiffness during Cell Reprogramming [RNA-seq]

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

Biphasic Regulation of Epigenetic State by Matrix Stiffness during Cell Reprogramming [ATAC-seq]

2023-12-19 | GSE250066 | GEO

Biphasic Regulation of Epigenetic State by Matrix Stiffness during Cell Reprogramming

Project description:Biphasic Regulation of Epigenetic State by Matrix Stiffness during Cell Reprogramming

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Mechanoresponsive genomic enhancers potentiate the cellular response to matrix stiffness

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-01-31 | GSE243765 | GEO

Premature termination of in vivo reprogramming leads to cancer development through altered epigenetic regulation

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-02-13 | E-GEOD-52304 | biostudies-arrayexpress

Large-scale epigenetic reprogramming is punctuated late during the evolution of pancreatic cancer progression

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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Biphasic response of cell invasion to matrix stiffness in three-dimensional biopolymer networks.

Project description:When cells come in contact with an adhesive matrix, they begin to spread and migrate with a speed that depends on the stiffness of the extracellular matrix. On a flat surface, migration speed decreases with matrix stiffness mainly due to an increased stability of focal adhesions. In a three-dimensional (3-D) environment, cell migration is thought to be additionally impaired by the steric hindrance imposed by the surrounding matrix. For porous 3-D biopolymer networks such as collagen gels, however, the effect of matrix stiffness on cell migration is difficult to separate from effects of matrix pore size and adhesive ligand density, and is therefore unknown. Here we used glutaraldehyde as a crosslinker to increase the stiffness of self-assembled collagen biopolymer networks independently of collagen concentration or pore size. Breast carcinoma cells were seeded onto the surface of 3-D collagen gels, and the invasion depth was measured after 3 days of culture. Cell invasion in gels with pore sizes >5 ?m increased with higher gel stiffness, whereas invasion in gels with smaller pores decreased with higher gel stiffness. These data show that 3-D cell invasion is enhanced by higher matrix stiffness, opposite to cell behavior in two dimensions, as long as the pore size does not fall below a critical value where it causes excessive steric hindrance. These findings may be important for optimizing the recellularization of soft tissue implants or for the design of 3-D invasion models in cancer research.

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ZFP708 maintains DNA methylation during epigenetic reprogramming in embryos

Project description:This SuperSeries is composed of the SubSeries listed below.

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Dynamic enhancer partitioning instructs Zdbf2 activation during epigenetic reprogramming

Project description:This SuperSeries is composed of the SubSeries listed below.

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