{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE305nnn/GSE305395/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE305395"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"PGC-1alpha pathway dysregulation disrupts myofiber specification in a mouse model of SBMA [AR113Q RNA-Seq]","description":"Skeletal muscle pathology is a critical but poorly understood contributor to neuromuscular degeneration in spinal and bulbar muscular atrophy (SBMA), a CAG/polyglutamine (polyQ) expansion disorder caused by mutation in the androgen receptor (AR). Using a gene-targeted SBMA mouse model, we applied single-nucleus RNA sequencing to identify a previously unrecognized, disease-specific population of skeletal muscle myonuclei that replace normal myonuclear subtypes. This transition was driven by dysregulation of the PGC-1α pathway, a central regulator of myofiber specification and metabolic identity. PGC-1α dysfunction in SBMA muscle was age-, hormone-, and polyQ length–dependent and was partially rescued by subcutaneous delivery of AR-targeted antisense oligonucleotides. Integrated ChIP-seq and RNA-seq analyses revealed that aberrant PGC-1α activity promoted the expression of a distinct set of myofiber specification genes while downregulating those defining healthy Type IIb and Type IIx myonuclei. We propose a model in which this dysfunction arose downstream of polyQ-mediated sequestration of PGC-1α cofactors MEF2, CREB, and CBP, leading to transcriptional reprogramming and cellular dysfunction. These findings implicate PGC-1α dysregulation as a key event linking AR polyQ expansion to skeletal muscle degeneration and suggest a shared mechanism for polyQ-mediated muscle pathology across related neurodegenerative diseases.","dates":{"publication":"2026/04/15"},"accession":"GSE305395","cross_references":{"GSM":["GSM9170977","GSM9170955","GSM9170976","GSM9170954","GSM9170975","GSM9170953","GSM9170974","GSM9170952","GSM9170951","GSM9170973","GSM9170972","GSM9170971","GSM9170970","GSM9170959","GSM9170958","GSM9170957","GSM9170956","GSM9170966","GSM9170965","GSM9170964","GSM9170963","GSM9170962","GSM9170961","GSM9170960","GSM9170969","GSM9170968","GSM9170967"],"GPL":["24247","34328"],"GSE":["305395"],"taxon":["Mus musculus"]}}