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Series GSE51933 Query DataSets for GSE51933
Status Public on Apr 23, 2014
Title Small RNA-sequencing of Fibro-Adipogenic Progenitors (FAPs) upon Histone Deacetylase inhibition in young mdx mice
Organism Mus musculus
Experiment type Non-coding RNA profiling by high throughput sequencing
Summary Fibro-adipogenic progenitors (FAPs) are emerging cellular components of the skeletal muscle regenerative environment. The alternative functional phenotype of FAPs - either supportive of muscle regeneration or promoting fibro-adipogenic degeneration - is a key determinant in the pathogenesis of muscular diseases, including Duchenne Muscular Dystrophy (DMD). However, the molecular regulation of FAPs is still unknown. We show here that an "HDAC-myomiR-BAF60 variant network" regulates the functional phenotype of FAPs in dystrophic muscles of mdx mice. Combinatorial analysis of gene expression microarray and genome-wide chromatin remodeling by Nuclease accessibility (NA)-seq revealed that HDAC inhibitors de-repress a "latent" myogenic program in FAPs from dystrophic muscles at early stages of disease progression. In these cells HDAC inhibition promoted the expression of two core components of the myogenic transcriptional machinery, MyoD and BAF60C, and upregulated the myomiRs (miRs) miR-1.2, miR-133 and miR-206, which target two alternative BAF60 variants (BAF60A and B) ultimately leading to the activation of a pro-myogenic program at the expense of the fibro-adipogenic phenotype. By contrast, FAPs from dystrophic muscles at late stages of disease progression displayed resistance to HDACi-induced chromatin remodeling at myogenic loci and fail to activate the pro-myogenic phenotype. These results reveal a previously unappreciated disease stage-specific bipotency of mesenchimal cells within the regenerative environment of dystrophic muscles. Resolution of such bi-potency by epigenetic interventions, such as HDACi, provides the molecular rationale for the in situ reprogramming of target cells to promote therapeutic regeneration of dystrophic muscles.
Overall design miRNA modulation upon Histone Deacetylase inhibition in Fibro-Adipogenic Progenitors (FAPs) derived from young mdx mice was evaluated by small RNA-sequencing in 2 controls and 2 treated samples
Contributor(s) Saccone V, Consalvi S, Madaro L, Fasanaro P, Puri PL
Citation(s) 24682306
Submission date Oct 30, 2013
Last update date May 15, 2019
Contact name Pier Lorenzo Puri
Phone +39-06-50170-3267
Organization name IRCCS Fondazione Santa Lucia
Lab Epigenetics & Regenerative Pharmacology
Street address Via del Fosso di Fiorano, 64
City Roma
ZIP/Postal code 00143
Country Italy
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (4)
GSM1255495 FAPs NT1
GSM1255496 FAPs NT2
GSM1255497 FAPs TSA1
BioProject PRJNA225833
SRA SRP032426

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Supplementary file Size Download File type/resource
GSE51933_miRNA_expression_FAPs.txt.gz 8.1 Kb (ftp)(http) TXT
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Processed data are available on Series record

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