Doctor James Ryall was awarded his PhD in the field of skeletal muscle physiology in 2006 at The University of Melbourne. In 2008 he was awarded a CJ Martin Overseas Biomedical Research Fellowship (NH&MRC) and from 2008-2013 he worked with Dr Vittorio Sartorelli at the National Institutes of Health in Bethesda, MD (USA) on trying to understand the links between intrinsic cell metabolism and the process of myogenic lineage commitment in skeletal muscle stem cells. This work was the first to provide the whole transcriptome of quiescent and actively proliferating muscle stem cells, and defined a process of metabolic programming.
In 2013 Dr Ryall returned to Australia and The University of Melbourne, where he is now a leading scientist within the Centre for Muscle Research (CMR). Dr Ryall’s current research lies in better understanding the link between skeletal muscle stem cells and their metabolic environment as they transition from quiescence to proliferating myogenic progenitor. A better understanding of the link between metabolism and cell identity will lead to improvements in stem cell transplantation and regenerative medicine, nuclear reprogramming, transdifferentiation, and stable ex vivo expansion of stem cells.
Skeletal muscle contains a resident population of somatic stem cells capable of both self-renewal and differentiation. The signals that regulate this important decision have yet to be fully elucidated. Here we show that in proliferating muscle stem cells extracellular monosaccharide availability regulates cell fate. Our results suggest that in conditions of reduced substrate availability, activated muscle stem cells prioritize the production of biomass and cell division over the supply of pyruvate to the TCA cycle. To meet ongoing energetic demands, muscle stem cells divert citrate/acetyl-CoA from histone acetylation to maintain TCA cycle anaplerosis. Interestingly, under these conditions of reduced histone acetylation muscle stem cells preferentially undergo asymmetric division, leading to increased Pax7+ and MyoD- muscle stem cells at the expense of Pax7- and MyoD+ muscle progenitors. Our results directly implicate the local metabolic milieu in the temporal regulation of transcription and the process of myogenic lineage progression.