Investigators: Anna Pakula PhD, Louis Kunkel PhD
Category: Research - Basic
Facioscapulohumeral muscular dystrophy-1 (FSHD-1) is the most prevalent muscular dystrophy affecting 1:8000, both children and adults. FSHD is progressive and leads to death of skeletal muscle cells in the facial, scapular, trunk and lower extremities muscles, resulting in muscle weakening. The age of onset, sequence of muscle affected and disease symptoms vary significantly between patients making FSHD-1 a heterogeneous disease.
FSHD-1 is an autosomal dominant disease caused by a contraction of the long arm of chromosome 4. That contraction leads to the chromatin opening and transcription of genes that are silenced in healthy individuals. To the one of these genes being uniquely activated in FSHD, belong DUX4 (double home box 4), a germline transcription factor, being very toxic to muscle cells even when expressed at the low frequencies. Dux4 is considered as a key disease player.
Although DUX4 has been explored, its exact function in muscle cells is not fully understood. DUX4 targets have been reported using microarray and RNA sequencing but the list of genes that are miss-regulated as a result of DUX4 expression differs from one study to the next. Moreover, RNA sequencing data obtained from FSHD cells and tissue, and from FSHD animal models, refer to RNA that derives from the pool of myogenic cells, and gives insight only into global gene transcriptomics, but does not provide any information about single cell transcriptomics of DUX4-expressing and DUX4 non-expressing cells. Moreover, the sequence of FSHD markers being expressed before, after and at the moment of DUX4 expression remain unknown. Therefore, we would like to focus our research on characterizing transcriptomics profile of single FSHD cells to get more insight into the molecular events happening in these dystrophic cells.