Investigating the epigenetic regulatory mechanisms involved in developmental programming of muscle stem cells – towards improving meat production from livestock

Substantial improvement in the efficiency of animal meat production (more meat from less animals) will be required for livestock farming to remain sustainable in the near future. Prenatal influences can have huge effects on muscle development and the ability of an animal to efficiently produce good quality meat later in life, through programming effects on body stem cell populations. An example of this is intra-uterine growth restriction (IUGR). IUGR is highly prevalent in the pig. It is also a leading cause of perinatal morbidity and mortality in humans. Impaired placental function results in reduced birth weight and organ maturity, and a propensity for later-life disease in IUGR babies. Importantly, through unidentified effects on tissue progenitor cells IUGR leads to reduced muscle formation and a propensity to accumulate body fat (1). In the pig, this results in poor piglet growth and reduced value of their meat, with significant financial consequences for the industry.  

Using a combination of RNA-sequencing and ATAC-sequencing in late-stage fetal tissues we recently identified hundreds of genes and regulatory genomic regions potentially involved in altered muscle development in IUGR pigs (2,3). This project will make further progress in that regard by:

1.     Undertaking the above genome-profiling approaches at the single cell level to determine how IUGR affects different cell populations in muscle.

2.     Functionally validating specific gene regulatory regions identified in 1, by testing their effects on muscle stem cell function using CRISPR/Cas9 technology.

The project will benefit from the supervisors’ combined expertise in livestock genomics and stem cells, to identify novel gene targets to be used in animal breeding programmes to increase the efficiency of meat production. The student will acquire a solid understanding of the areas above and will become proficient in a variety of cell/molecular laboratory techniques (single-cell ATAC-seq and RNA-Seq, CRISPR/Cas9, FACS, qPCR, immunochemistry).