Abstract The “canonical” function of Pax7+ muscle stem cells (satellite cells) during hypertrophic growth of adult muscle fibers is myonuclear donation via fusion to support increased transcriptional output. In recent years, however, emerging evidence suggests that satellite cells play an important secretory role in promoting load-mediated growth. Utilizing genetically modified mouse models of delayed satellite cell fusion and in vivo extracellular vesicle tracking, we provide evidence for satellite cell communication to muscle fibers during hypertrophy. Myogenic progenitor cell extracellular vesicle-mediated communication to myotubes in vitro influences extracellular matrix (ECM)-related gene expression, which is congruent with in vivo overload experiments involving satellite cell depletion, as well as in silico analyses. Satellite cell-derived extracellular vesicles can transfer a Cre-induced, cytoplasmic-localized fluorescent reporter to muscle cells as well as miRNAs that regulate ECM genes such as matrix metalloproteinase 9 (Mmp9), which may facilitate growth. Delayed satellite cell fusion did not limit long-term load-induced muscle hypertrophy indicating that early fusion-independent communication from satellite cells to muscle fibers is an under-appreciated aspect of satellite cell biology. We cannot exclude the possibility that satellite cell-mediated myonuclear accretion is necessary to maintain prolonged growth, specifically in the later phases of adaptation, but these data collectively highlight how extracellular vesicle delivery from satellite cells can directly contribute to mechanical load-induced muscle fiber hypertrophy, independent of cell fusion to the fiber.

Highlights Widespread myogenic cell communication in muscle during mechanical overload (MOV) Extracellular vesicles from myogenic progenitors repress Wisp1 in fibrogenic cells Fibrogenic fate and chemokines are influenced by satellite cells early during MOV Prior to fusion, satellite cell communication regulates long-term hypertrophy

Efficient delivery of therapeutics across the cell membrane to the interior of the cell remains a challenge both in vitro and in vivo. Here, we demonstrate that vesicles derived from cellular membranes can be efficiently loaded with cargo that can then be delivered to the interior of the cell. These vesicles demonstrated cell-targeting specificity as well as the ability to deliver a wide range of different cargos. We utilized this approach to deliver both lipophilic and hydrophilic cargos including therapeutics and DNA in vitro. We further demonstrated in vivo targeting and delivery using fluorescently labeled vesicles to target tumor xenografts in an animal. Cell-derived vesicles can be generated in high yields and are easily loaded with a variety of cargos. The ability of these vesicles to specifically target the same cell type from which they originated provides an efficient means of delivering cargo, such as therapeutics, both in vitro and in vivo.

Nicotine is a highly addictive compound present in tobacco, which causes the release of dopamine in different regions of the brain. Recent studies have shown that astrocytes express nicotinic acetylcholine receptors (nAChRs) and mediate calcium signaling. In this study, we examine the morphological and functional adaptations of astrocytes due to nicotine exposure. Utilizing a combination of fluorescence and atomic force microscopy, we show that nicotine‐treated astrocytes exhibit time‐dependent remodeling in the number and length of both proximal and fine processes. Blocking nAChR activity with an antagonist completely abolishes nicotine's influence on astrocyte morphology indicating that nicotine's action is mediated by these receptors. Functional studies show that 24‐hr nicotine treatment induces higher levels of calcium activity in both the cell soma and the processes with a more substantial change observed in the processes. Nicotine does not induce reactive astrocytosis even at high concentrations (10 μM) as determined by cytokine release and glial fibrillary acidic protein expression. We designed tissue clearing experiments to test whether morphological changes occur in vivo using astrocyte specific Aldh1l1‐tdTomato knock in mice. We find that nicotine induces a change in the volume of astrocytes in the prefrontal cortex, CA1 of the hippocampus, and the substantia nigra. These results indicate that nicotine directly alters the functional and morphological properties of astrocytes potentially contributing to the underlying mechanism of nicotine abuse.

We report on transport signatures of eight distinct bubble phases in the N = 3 Landau level of a AlxGa1−xAs/Al0.24Ga0.76As quantum well with x = 0.0015. These phases occur near partial filling factors ν ⋆ ≈ 0.2 (0.8) and ν ⋆ ≈ 0.3 (0.7) and have M = 2 and M = 3 electrons (holes) per bubble, respectively. We speculate that a small amount of alloy disorder in our sample helps to distinguish these broken symmetry states in low-temperature transport measurements.