In our younger years our rampant metabolism meant we could eat what we wanted with little or no consequences. However, as we get older, our metabolism somehow gets “reprogrammed”, meaning all that yummy bad stuff does nothing for our energy levels or our waistlines! But why do we face this fate?
A delectable new study from the laboratory of Vittorio Sartorelli has now smartly linked changes in cellular metabolism and energy production to changes in stem cell fate, all mediated through an epigenetic modifier. Specifically, researchers have found that when mouse skeletal muscle stem cells (or satellite cells – SCs) change from their normal dormant quiescent state to the activated proliferating state, their metabolism becomes reprogrammed. This metabolic change then modifies the activity of a histone deacetylase which alters gene expression and stem cell fate.
During in vitro culture of SCs:
- A change from quiescence to proliferation reprograms cellular metabolism from aerobic respiration as an energy supply, to anaerobic respiration.
- This change decreases the levels of cellular nicotinamide adenine dinucleotide (NAD+) levels, a by-product of aerobic respiration, leading to the downregulation of Sirtuin 1 (Sirt1) class III histone deacetylase activity.
- This reduction in activity boosts H4K16 acetylation in SCs, and leads to the activation of muscle specific gene transcription and a change in cell fate from a stem-cell like state to a more mature muscle state.
Moving into mouse in vivo experimentation:
- Skeletal-muscle specific knock out of Sirt1 increased H4K16 acetylation in SCs and led to signs of early differentiation to a more mature cell fate.
- These mice also presented with a smaller overall size, reduced muscle myofiber size, reduced muscle regeneration after injury, and deregulated expression of muscle developmental genes.
The authors have deliciously shown that quick changes to cellular metabolism can regulate epigenetic modifications to alter stem cell fate. If only we could reprogram our bodily metabolism in such an elegant manner!
Until then get your fill over at Cell Stem Cell, January 2015.