Does Dystrophin Restoration Reverse Epigenetic and Transcriptional Pathogenic Features in Duchenne Muscular Dystrophy?
Abstract
The purpose of this project is to investigate the effect of dystrophin loss on 3D genome organization and gene expression output of skeletal myofibers, and determine whether recovery of expression of a short form of dystrophin (micro-dystrophin) currently used in clinical trial with boys affected by Duchenne Muscular Dystrophy (DMD) can restore in full or partly the original 3D nuclear landscape and gene expression. The scope of this research is the identification of pathological alterations in chromatin interactions than impair the expression of genes implicated in the pathogenesis of DMD. We have successfully established a experimental pipelines that allows the isolation of myonuclei from a mouse model of DMD (mdx mice) as well as from DMD skeletal muscles derived from iPSCs. We have generated datasets of RNAseq, ATACseq and HiChIP from cultures of DMD muscles (or wildtype controls), before or after micro-dystrophin re-expression, that have been partly analyzed, as well as prepared samples from mdx mice that have been sent out for sequencing.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1194883
Entities
People
- Pier L. Puri