Comment[ArrayExpressAccession] E-GEOD-51933 MAGE-TAB Version 1.1 Public Release Date 2014-04-23 Investigation Title Small RNA-sequencing of Fibro-Adipogenic Progenitors (FAPs) upon Histone Deacetylase inhibition in young mdx mice Comment[Submitted Name] Small RNA-sequencing of Fibro-Adipogenic Progenitors (FAPs) upon Histone Deacetylase inhibition in young mdx mice Experiment Description 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. 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 Term Source Name ArrayExpress EFO Term Source File http://www.ebi.ac.uk/arrayexpress/ http://www.ebi.ac.uk/efo/efo.owl Person Last Name Puri Saccone Consalvi Madaro Fasanaro Puri Person First Name Pier Lorenzo Valentina Silvia Luca Pasquale Pier Person Mid Initials L Person Email pl.puri@hsantalucia.it Person Affiliation IRCCS Fondazione Santa Lucia Person Phone +39-06-50170-3267 Person Address IRCCS Fondazione Santa Lucia, Via del Fosso di Fiorano, 64, Roma, Italy Person Roles submitter Protocol Name P-GSE51933-3 P-GSE51933-1 P-GSE51933-2 Protocol Description Fastq files were analyzed with miRDEEP* using the following parameters: genome mm10, adapter TGGAATTCTCGGGTGCCAAGG, miR length 18 to 23, min phred 20, max multimap 101, min reads 5, min score -10 the expression level were calculated as the number of reads covering the mature miRNA region Genome_build: mm10 Supplementary_files_format_and_content: the expression level contain the number of reads covering the mature miRNA region 1.5 month old C57Bl6 mdx mice were treated for 15 days with daily i.p. injections of Trichostatin A, TSA (0.6 mg/Kg/day; Sigma) freshly isolated cells were flash frozen on dry ice, and RNA was harvested using Trizol reagent small-RNA libraries were prepared for sequencing using standard Illumina protocols Protocol Type normalization data transformation protocol sample treatment protocol nucleic acid library construction protocol Experimental Factor Name COMPOUND Experimental Factor Type compound Publication Title HDAC-regulated myomiRs control BAF60 variant exchange and direct the functional phenotype of fibro-adipogenic progenitors in dystrophic muscles. Publication Author List Saccone V, Consalvi S, Giordani L, Mozzetta C, Barozzi I, Sandon� M, Ryan T, Rojas-Mu�oz A, Madaro L, Fasanaro P, Borsellino G, De Bardi M, Frig� G, Termanini A, Sun X, Rossant J, Bruneau BG, Mercola M, Minucci S, Puri PL PubMed ID 24682306 Publication DOI 10.1101/gad.234468.113 Comment[SecondaryAccession] GSE51933 Comment[GEOReleaseDate] 2014-04-23 Comment[ArrayExpressSubmissionDate] 2013-10-30 Comment[GEOLastUpdateDate] 2014-04-23 Comment[AEExperimentType] RNA-seq of non coding RNA Comment[AdditionalFile:Data1] GSE51933_miRNA_expression_FAPs.txt Comment[SecondaryAccession] SRP032426 Comment[SequenceDataURI] http://www.ebi.ac.uk/ena/data/view/SRR1022281-SRR1022284 SDRF File E-GEOD-51933.sdrf.txt