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Series GSE211422 Query DataSets for GSE211422
Status Public on Mar 28, 2023
Title The chromatin remodeler Brg1 directs smooth muscle-derived adventitial progenitor-to-myofibroblast differentiation and in situ vascular fibrosis [CUT&RUN]
Organism Mus musculus
Experiment type Other
Summary Smooth muscle-derived Sca1+ adventitial progenitor cells are tissue resident, multipotent stem cells that contribute to progression of vascular remodeling and fibrosis. Upon acute vascular injury, AdvSca1-SM cells differentiate into myofibroblasts and are embedded in perivascular collagen and matrix tissue. While the phenotypic properties of AdvSca1-SM-derived myofibroblasts have been defined, the underlying epigenetic regulators driving the differentiation trajectory of AdvSca1-SM cells to myofibroblasts are unclear. Here we show that the chromatin remodeler Smarca4/Brg1 facilitates AdvSca1-SM myofibroblast differentiation. Brg1 mRNA and protein was upregulated in AdvSca1-SM cells in vivo after acute vascular injury and pharmacological inhibition of the Brg1 bromodomain by the small molecule PFI-3 attenuated perivascular fibrosis and adventitial expansion. TGF-β1 stimulation of AdvSca1-SM cells in vitro reduced expression of stemness-related genes while inducing expression of myofibroblast genes that was associated with enhanced contractility; Brg1 inhibition blocked TGF-β1-induced phenotypic transition. Mechanistically, TGF-β1 promoted redistribution of Brg1 from distal regulatory sequences of stemness-related genes and recruitment of Brg1 to promoters of myofibroblast-related genes. This recruitment of Brg1 to myofibroblast genes was blocked in the presence of PFI-3. These data shed insight into epigenetic regulation of resident vascular progenitor cell differentiation and support that manipulating AdvSca1-SM phenotype will provide important anti-fibrotic clinical benefit.
 
Overall design To obtain differential binding analysis of Brg1-DNA interactions in the AdvSca1-SM genome of AdvSca1-SM cells maintained in the following experimental conditions for 72 hours: stem/baseline, 5ng/mL TGF-B, or 5ng/mL TGF-B + 50uM PFI-3.
 
Contributor(s) Jolly AJ, Lu S, Dubner AM, Strand KA, Mutryn MF, Pilotti-Riley A, Danis EP, Nemenoff RA, Moulton KS, Majesky MW, Weiser-Evans MC
Citation(s) 36976650
Submission date Aug 17, 2022
Last update date Mar 31, 2023
Contact name Mary C.M. Weiser-Evans
E-mail(s) Mary.weiser@ucdenver.edu
Phone 303-724-4846
Organization name University of Colorado Anschutz Medical Campus
Department Renal Diseases & Hypertension
Lab Dr. Mary C.M. Weiser-Evans
Street address 12700 East 19th Avenue, C281
City Aurora
State/province CO
ZIP/Postal code 80045
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (3)
GSM6469825 Stem
GSM6469826 Tgfb
GSM6469827 Tgfb_PFI3
This SubSeries is part of SuperSeries:
GSE211423 The chromatin remodeler Brg1 directs smooth muscle-derived adventitial progenitor-to-myofibroblast differentiation and in situ vascular fibrosis.
Relations
BioProject PRJNA870289

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
GSE211422_RAW.tar 712.6 Mb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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