Chronic Chromatin Activation in Aged Muscle Stem Cells

Chromatin is the packaged structure of DNA in the cell nucleus, and its arrangement determines which genes can be expressed. Researchers here show that chromatin is more accessible to expression in aged muscle stem cells, a part of the change in cell behavior. Whether this can be reversed by partial reprogramming is an interesting question. It seems plausible given that reprogramming changes gene expression patterns in cells, reverting them to a more youthful state, and certainly something that can be tested.

Adult stem cells are essential for tissue regeneration and homeostasis maintenance. Skeletal muscle possesses a remarkable regeneration capacity after acute injury because of its resident stem cells, muscle stem cells, or satellite cells (SCs). pon stimuli such as acute injury, quiescent SCs exit from quiescence to activate and re-enter the cell cycle for proliferation. They will further differentiate to repair the damaged tissue. Some activated SCs will return to quiescence through the self-renewal process to replenish the stem cell pool.

Eukaryotic DNA is highly organized into a nuclear structure called chromatin. The accessibility to the regulatory DNA elements restrains the gene expression, therefore defining the cell identity. In this study, we examined the chromatin accessibility changes of SCs, from quiescence exit, early activation, and regeneration, showing the trajectory of chromatin environment changes for SC activation in young and aged conditions. We showed that the chromatin environment of SCs is very compact during quiescence, becomes highly accessible on early activation, and gradually re-establish the compact state after long-term regeneration. We found that the old SCs exhibit a much more open chromatin environment, suggesting that the old SCs exhibit a chronically activated chromatin state.