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Status |
Public on Dec 19, 2023 |
Title |
Biphasic Regulation of Epigenetic State by Matrix Stiffness during Cell Reprogramming [ATAC-seq] |
Organism |
Mus musculus |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
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.
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Overall design |
To investigate the effect of matrix stiffness on the epigenetic state during induced neuronal reprogramming, mouse dermal fibroblasts were cultured on polyacrylamide hydrogels of varying stiffness or glass, which served as control, for 3 days and then samples were collected for ATAC-seq.
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Contributor(s) |
Song Y, Soto J, Wu Y, Li S |
Citation(s) |
38354231 |
BioProject |
PRJNA1051591 |
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Submission date |
Dec 13, 2023 |
Last update date |
Mar 19, 2024 |
Contact name |
Song Li |
E-mail(s) |
songli@ucla.edu
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Organization name |
UCLA
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Street address |
404 Westwood Plaza, Eng VI
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City |
Los Angeles |
State/province |
California |
ZIP/Postal code |
90095 |
Country |
USA |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (6)
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This SubSeries is part of SuperSeries: |
GSE250069 |
Biphasic Regulation of Epigenetic State by Matrix Stiffness during Cell Reprogramming |
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