ABSTRACT
Cellular senescence is the irreversible arrest of normally dividing cells and is driven by the cell cycle inhibitors Cdkn2a, Cdkn1a, and Trp53. Senescent cells are implicated in chronic diseases and tissue repair through their increased secretion of pro-inflammatory factors known as the senescence-associated secretory phenotype (SASP). Here, we use spatial transcriptomics and single-cell RNA sequencing (scRNAseq) to demonstrate that cells displaying senescent characteristics are "transiently" present within regenerating skeletal muscle and within the muscles of D2-mdx mice, a model of Muscular Dystrophy. Following injury, multiple cell types including macrophages and fibrog-adipogenic progenitors (FAPs) upregulate senescent features such as senescence pathway genes, SASP factors, and senescence-associated beta-gal (SA-ß-gal) activity. Importantly, when these cells were removed with ABT-263, a senolytic compound, satellite cells are reduced, and muscle fibers were impaired in growth and myonuclear accretion. These results highlight that an "acute" senescent phenotype facilitates regeneration similar to skin and neonatal myocardium.
Subject(s)
Cellular Senescence , Senotherapeutics , Animals , Cellular Senescence/physiology , Mice , Mice, Inbred mdx , Muscle, Skeletal , Stem Cells/metabolismABSTRACT
Reparable sonoporation was observed in Jurkat lymphocytes in suspension exposed to a vibrating Mason horn tuned to 21.4 KHz. The diameter of the horn tip was 400 microm and its transverse displacement amplitude was 7.8 microm. It was found that the shear stress associated with microstreaming surrounding the Mason-horn tip was the primary reason for the cell reparable sonoporation. The threshold shear stress was determined to be 12 +/- 4 Pa for exposure time up to 7 min. It was also found that the shorter the exposure time, the greater the threshold.
