What would you do to ensure your immortality? Drink a potion? Cast a spell? Or even set out on an expedition to find the fountain of youth? Researchers from the Adult Stem Cell Technology Centre in Boston, USA have discovered that adult stem cells in the mouse have another more intricate strategy towards living forever – specific epigenetic modifications – using two novel techniques.
The group studied adult hair follicle stem cells (HFSCs) which, like other adult stem cells, non-randomly place one DNA strand in self-renewing stem cells (“immortal”), while the other DNA strand is placed in the differentiated progeny (“mortal”). Excitingly, upon studying this type of division in detail, the group discovered that immortal DNA strands contained higher levels of a specialized histone protein, histone H2AZ, and high levels of two histone modifications, H3K4me3 and H3K27me3.
The group firstly amplified the numbers of HFSCs by addition of xanthine to the growth medium; a novel methodology to address the scarcity of adult stem cells. This technique, known as SACK (suppression of asymmetric cell kinetics) boosts the production of self-renewing HFSCs at the cost of differentiated daughter cells (symmetrical division). Removal of xanthine, to allow for asymmetrical cell division, followed by cell cycle arrest using cytochalasin D, led to the production of large numbers of cells with two nuclei. One nucleus represented the stem cell progeny with the immortal DNA strand, and the other nucleus represented the differentiated daughter cell with the mortal DNA strands.
Using these cells the authors discovered that the immortal strand contained higher H2AZ, allowing them to use this as a marker to identify and analyze the immortal strand. From this analysis they found:
- much higher levels of H3K4me3 and H3K27me3 – marks that are found at gene promoters specifically in stem cells and allows cells to self-renew – on the immortal strand compared to the mortal strand
- that H2AZ detection agreed with previous techniques 89% of the time, suggesting that this new technique is highly utile.
The use of the histone H2A variant H2A.Z to identify immortal chromosomes forgoes other retrospective techniques, which generally require chromosome denaturants that may obscure molecular investigations.
While this study highlights that there are distinct epigenetic differences between immortal and mortal DNA strands, the how and why remain a mystery. The novel techniques applied in his study will hopefully lead to further discoveries, both in vitro and in vivo, and perhaps through targeting epigenetic modifications we may all cheat death!