Regulation of Fat Storage and Reproduction by Krüppel-Like Transcription Factor KLF3 and Fat-Associated Genes in Caenorhabditis elegans

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Transcriptomal Insights of Heart Failure from Normality to Recovery.

Current management of heart failure (HF) is centred on modulating the progression of symptoms and severity of left ventricular dysfunction. However, specific understandings of genetic and molecular targets are needed for more precise treatments. To attain a clearer picture of this, we studied transcriptome changes in a chronic progressive HF model. Fifteen sheep (Ovis aries) underwent supracoronary aortic banding using an inflatable cuff. Controlled and progressive induction of pressure overload in the LV was monitored by echocardiography. Endomyocardial biopsies were collected throughout the development of LV failure (LVF) and during the stage of recovery. RNA-seq data were analysed using the PANTHER database, Metascape, and DisGeNET to annotate the gene expression for functional ontologies. Echocardiography revealed distinct clinical differences between the progressive stages of hypertrophy, dilatation, and failure. A unique set of transcript expressions in each stage was identified, despite an overlap of gene expression. The removal of pressure overload allowed the LV to recover functionally. Compared to the control stage, there were a total of 256 genes significantly changed in their expression in failure, 210 genes in hypertrophy, and 73 genes in dilatation. Gene expression in the recovery stage was comparable with the control stage with a well-noted improvement in LV function. RNA-seq revealed the expression of genes in each stage that are not reported in cardiovascular pathology. We identified genes that may be potentially involved in the aetiology of progressive stages of HF, and that may provide future targets for its management

Identification of the tetraspanin CD82 as a new barrier to xenotransplantation

Significant immunological obstacles are to be negotiated before xenotransplantation becomes a clinical reality. An initial rejection of transplanted vascularized xenograft is attributed to Galα1,3Galβ1,4GlcNAc-R (Galα1,3-Gal)-dependent and -independent mechanisms. Hitherto, no receptor molecule has been identified that could account for Galα1,3-Gal-independent rejection. In this study, we identify the tetraspanin CD82 as a receptor molecule for the Galα1,3-Gal-independent mechanism. We demonstrate that, in contrast to human undifferentiated myeloid cell lines, differentiated cell lines are capable of recognizing xenogeneic porcine aortic endothelial cells in a calcium-dependent manner. Transcriptome-wide analysis to identify the differentially expressed transcripts in these cells revealed that the most likely candidate of the Galα1,3-Gal-independent recognition moiety is the tetraspanin CD82. Abs to CD82 inhibited the calcium response and the subsequent activation invoked by xenogeneic encounter. Our data identify CD82 on innate immune cells as a major "xenogenicity sensor" and open new avenues of intervention to making xenotransplantation a clinical reality