Mouse anti-Human ITGB6 monoclonal antibody, clone 5D4

Mechanism controlling myo-adipogenic balance in skeletal muscle is of great significance for human skeletal muscle dysfunction and myopathies as well as livestock meat quality. In the present study, two cell subpopulations with particular potency of adipogenic or myogenic differentiation were isolated from neonatal porcine longissimus dorsi using the preplate method to detect mechanisms underlying distinct fate commitment of myogenic and adipogenic cells in skeletal muscle. Both cells share a common surface expression profile of CD29(+)CD31-CD34-CD90(+)CD105(+), verifying their mesenchymal origin. A total of 448 differentially expressed genes (DEGs) (FDR <0.05 and |log(2) FC|>= 1) between two distinct cells were identified via RNA-seq, including 358 up-regulated and 90 down-regulated genes in myogenic cells compared with adipogenic cells. The results of functional annotation and enrichment showed that 42 DEGs were implicated in cell differentiation, among them PDGFRa, ITGA3, ITGB6, MLCK and MLC acted as hubs between environment information processing and cellular process, indicating that the interaction of the two categories exerts an important role in distinct fate commitment of myogenic and adipogenic cells. Particularly, we are first to show that up-regulation of intracellular Ca2+-MLCK and Rho-DMPK, and subsequently elevated MLC, may contribute to the distinct commitment of myogenic and adipogenic lineages via mediating cytoskeleton dynamics.

Mouse models are useful for studying cigarette smoke (CS)-induced chronic pulmonary pathologies such as lung emphysema. To enhance translation of large-scale omics data from mechanistic studies into pathophysiological changes, we have developed computational tools based on reverse causal reasoning (RCR). In the present study we applied a systems biology approach leveraging RCR to identify molecular mechanistic explanations of pathophysiological changes associated with CS-induced lung emphysema in susceptible mice. The lung transcriptomes of five mouse models (C57BL/6, ApoE (-/-) , A/J, CD1, and Nrf2 (-/-) ) were analyzed following 5-7 months of CS exposure. We predicted 39 molecular changes mostly related to inflammatory processes including known key emphysema drivers such as NF-kappa B and TLR4 signaling, and increased levels of TNF-alpha, CSF2, and several interleukins. More importantly, RCR predicted potential molecular mechanisms that are less well-established, including increased transcriptional activity of PU.1, STAT1, C/EBP, FOXM1, YY1, and N-COR, and reduced protein abundance of ITGB6 and CFTR. We corroborated several predictions using targeted proteomic approaches, demonstrating increased abundance of CSF2, C/EBP alpha, C/EBP beta, PU.1, BRCA1, and STAT1. These systems biology-derived candidate mechanisms common to susceptible mouse models may enhance understanding of CS-induced molecular processes underlying emphysema development in mice and their relevancy for human chronic obstructive pulmonary disease.