Delta like 1 (DLK1) has been proposed to act as a regulator of cell fate determination and is linked to the development of various tissues including skeletal muscle. Herein we further investigated DLK1 expression during skeletal muscle remodeling. Although practically absent in normal adult muscle, DLK1 was upregulated in all human myopathies analyzed, including Duchenne-and Becker muscular dystrophies. Substantial numbers of DLK1 1 satellite cells were observed in normal neonatal and Duchenne muscle, and furthermore, myogenic DLK1 1 cells were identified during muscle regeneration in animal models in which the peak expression of Dlk1 mRNA and protein coincided with that of myoblast differentiation and fusion. In addition to perivascular DLK11 cells, interstitial DLK1 1 cells were numerous in regenerating muscle, and in agreement with colocalization studies of DLK1 and CD90/DDR2, qPCR of fluorescence-activated cell sorting DLK1 1 and DLK1 2 cells revealed that the majority of DLK11 cells isolated at day 7 of regeneration had a fibroblast-like phenotype. The existence of different DLK11 populations was confirmed in cultures of primary derived myogenic cells, in which large flat nonmyogenic DLK11 cells and small spindle-shaped cells coexpressing DLK1 and muscle-specific markers were observed. Myogenic differentiation was achieved when sorted DLK11 cells were cocultured together with primary myoblasts revealing a myogenic potential that was 10% of the DLK1 2 population. Transplantation of DLK1 1 cells into lacerated muscle did, however, not give rise to DLK1 1 cell-derived myofibers. We suggest that the DLK1 1 subpopulations identified herein each may contribute at different levels/time points to the processes involved in muscle development and remodeling. STEM CELLS 2009;27:898-908 Disclosure of potential conflicts of interest is found at the end of this article.

This study shows that fat accumulates intramyocellulary while glycogen stores are simultaneously reduced in obese subjects with Type II (non-insulin-dependent) diabetes mellitus. Quantitatively, a major component of the excessive lipid accumulation could be secondary in origin, related to the diabetic state in itself, although a contribution from the altered insulin action cascade of obesity and diabetes cannot be excluded. In both groups significant positive relations were found between circulating and intramyocellular lipid.

of a thirty-nine-year-old dens fracture causing myelopathy

Background Rotator cuff (RC) tears are associated with RC muscle atrophy and changes in composition that are crucial to the prognosis of RC repair. The aim of this study was to characterize muscle fiber composition in the supraspinatus (SS) muscle under tear conditions. Methods Muscle biopsies were obtained from 21 patients undergoing surgery for an RC tendon tear. Biopsies were obtained from the musculotendinous junction of the SS muscle, and control biopsies were harvested from the deltoid muscle (DT). Biopsies were immunohistochemically processed for detection of type 1 (slow type) and type 2 (fast type) fibers and analyzed using unbiased, stereological principles. We counted the total numbers of type 1 and 2 muscle fibers/mm 2 , and fiber diameter was used to estimate muscle fiber atrophy and hypertrophy. Results We found significantly more type 2 cells/mm 2 in the SS compared with the DT ( P < .01). In addition, we found a significantly higher fraction of type 1 fibers than type 2 fibers in the DT ( P < .01), whereas both fiber types were equally present in the SS. The diameters of SS cells were generally smaller than those of DT cells. Atrophy of especially SS type 2 fibers was also demonstrated. Fiber atrophy was more pronounced in men than women. Conclusion The changes in the composition of SS muscle cell types suggest a shift from type 1 to type 2 muscle fibers and atrophy of both type 1 and 2 fibers. This composition indicates loss of endurance and rapid fatigue of the SS muscle under RC tear conditions.

The identification of novel targets is of paramount importance to develop more effective drugs and improve the treatment of non-small cell lung cancer (NSCLC), the leading cause of cancer-related deaths worldwide. Since cells alter their metabolic rewiring during tumorigenesis and along cancer progression, targeting key metabolic players and metabolism-associated proteins represents a valuable approach with a high therapeutic potential. Metabolic fitness relies on the functionality of heat shock proteins (HSPs), molecular chaperones that facilitate the correct folding of metabolism enzymes and their assembly in macromolecular structures. Here, we show HSPD1 (HSP60) as a survival gene ubiquitously expressed in NSCLC and associated with poor patients' prognosis. HSPD1 knockdown or its chemical disruption by the small molecule KHS101 induces a drastic breakdown of oxidative phosphorylation, and suppresses cell proliferation both in vitro and in vivo. By combining drug profiling with transcriptomics and through a whole-genome CRISPR/Cas9 screen, we demonstrate that HSPD1-targeted anti-cancer effects are dependent on OXPHOS and validated molecular determinants of KHS101 sensitivity, in particular, the creatine-transporter SLC6A8 and the subunit of the cytochrome c oxidase complex COX5B. These results highlight mitochondrial metabolism as an attractive target and HSPD1 as a potential theranostic marker for developing therapies to combat NCSLC.