UCLA

The transition of muscle stem cells, known as satellite cells (SCs), from a quiescent state to an active, proliferative, and myogenic state facilitates muscle repair following injury. We tested the hypothesis that hemizygous expression of Jmjd3, a H3K27me3 histone demethylase, in SCs following acute injury would affect various stages of muscle regeneration. Our findings show there is an increased proportion of H3K27me2/3+/Pax7+ cells out of total Pax7+ cells in acutely injured Jmjd3 hemizygous mice, suggesting the mutation reduced H3K27me2/3 demethylation. We next investigated muscle fiber growth and myonuclei per muscle fiber to determine myocyte fusion. Our data indicate the Jmjd3 mutation diminished the average cross-sectional area (CSA) of muscle fibers after injury, while having no effect on myonuclei per muscle fiber suggesting myocyte fusion was not affected. We then investigated myocyte proliferation and found the Jmjd3 hemizygous mutation reduced the proportion of Ki67+/Pax7+ cells out of total Pax7+ cells, suggesting a reduction in injured muscle compared to Jmjd3 control mice. Our results show attenuation of H3K27me3 histone demethylation, muscle fiber growth, and SC proliferation when SC Jmjd3 expression is reduced, thus affecting muscle regeneration.