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Series GSE250066 Query DataSets for GSE250066
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
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.
 
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.
 
Contributor(s) Song Y, Soto J, Wu Y, Li S
Citation(s) 38354231
BioProject PRJNA1051591
Submission date Dec 13, 2023
Last update date Mar 19, 2024
Contact name Song Li
E-mail(s) songli@ucla.edu
Organization name UCLA
Street address 404 Westwood Plaza, Eng VI
City Los Angeles
State/province California
ZIP/Postal code 90095
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (6)
GSM7973471 Glass_rep1_ATAC
GSM7973472 Glass_rep2_ATAC
GSM7973473 1_kPa_rep1_ATAC
This SubSeries is part of SuperSeries:
GSE250069 Biphasic Regulation of Epigenetic State by Matrix Stiffness during Cell Reprogramming

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE250066_RAW.tar 2.8 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA

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