Project description:We report bulk scRNAseq data obtained from 2 P6 mice. Input was isolated epithelium cells of the small intestine in a 2cm segment of the jejunum and 2 cm segment in the ileum of the same mouse, 1 male and 1 female were included in the analysis.
Project description:Background: Although chamber specialization is critical for proper cardiac function, a comprehensive, genome-wide analysis of the cardiac transcriptome, including identification of regional differences in mRNA and lncRNA expression patterns for the four chambers and interventricular septum of the non-failing human heart, has not been performed. Methods and Results: mRNA and long noncoding RNA (lncRNA) transcriptional profiling of the left (LA) and right (RA) atria, left (LV) and right (RV) ventricles, and the interventricular septum (IVS) of non-failing human hearts (N=8) was performed by deep sequencing. Analysis of the mRNA and lncRNA expression profiles revealed that the different regions of the heart are distinct. Differential expression analysis of paired tissue samples identified 5,747 mRNAs and 2,794 lncRNAs with chamber-enriched expression patterns. The largest differences in mRNA and lncRNA expression were evident between atria and ventricular samples, including regional differences in ~20% of all cardiac expressed mRNA and lncRNA transcripts. Regional differences in mRNA and lncRNA expression were also evident, although to a lesser extent, between the LA and RA, and between the LV, RV and IVS. Gene ontology classification of differentially expressed gene sets revealed regional differences in chamber specialization, including differences in signaling, metabolism, and muscle contraction. Sex differences in mRNA and lncRNA gene expression profiles were also identified between male and female LA and RA samples. Conclusions: There are marked regional differences in the mRNA and lncRNA expression profiles in non-failing adult human heart, and are associated with chamber specialization.
Project description:Purpose: In the C57BL/6J mouse retina, hyperoxia-induced degeneration of photoreceptors shows strong regional variation, beginning at a locus ~0.5mm inferior to the optic disc. To identify gene expression differences that might underlie this variability in vulnerability, we have used microarray techniques to describe regional (superior-inferior) variations in gene expression in the retina.
Project description:The role of shear stress, the frictional force of blood flow, on the endothelium has been well documented. Differences in shear stress can have profound effects on endothelial and blood vessel biology. Endothelial cells (ECs), termed endocardial ECs, line the heart chambers and are exposed to complex shear stress patterns. While it has been demonstrated that shear stress is important for heart development, little has been shown on the role of shear stress on adult ECs. 4D-MRI studies demonstrate regional differences in blood residence time. We sought to determine the effect of regional differences in endocardial shear stress on the endocardial transcriptome using RNA sequencing (RNA-seq) on 3 different regions (apex, mid-ventricle, outflow tract) from 8 adult pigs, for a total of 24 RNA-seq assays.
Project description:Digested dietary fats are taken up, processed and transported by enterocytes to supply the body with lipids. Most absorbed lipids are assembled into pre-chylomicrons in the endoplasmic reticulum (ER) of enterocytes, which are then transported to the Golgi for maturation and subsequent secretion to the circulation. The role of mitochondria in regulating intestinal lipid transport remains unknown. Here we show that mitochondrial dysfunction in enterocytes inhibits chylomicron production and the transport of dietary lipids to peripheral organs. Mice with intestinal epithelial cell (IEC)-specific ablation of the mitochondrial-specific aspartyl - tRNA synthetase DARS2, as well as of the respiratory chain subunit SDHA or the assembly factor COX10 failed to thrive and showed massive accumulation of lipids within large lipid droplets (LDs) in enterocytes of the proximal small intestine (SI). Feeding a fat-free diet inhibited the formation of LDs in DARS2-deficient enterocytes, showing that accumulating lipids derive mostly from digested fat. Furthermore, metabolic tracing studies revealed impaired transport of dietary lipids to peripheral organs in mice lacking DARS2 in IECs. Moreover, DARS2-deficient enterocytes showed a distinct lack of mature chylomicrons concomitant with a disorganisation of the Golgi apparatus, suggesting that impaired ER to Golgi trafficking underlies impaired chylomicron production and secretion. Taken together, these results revealed a vital role of mitochondria in regulating dietary lipid transport in enterocytes, which is relevant for understanding the intestinal and nutritional defects observed in patients with mitochondrial defects.
Project description:The intestinal epithelium is the first line of defence against invasive enteric pathogens. Removal of infected cells by exfoliation prevents mucosal translocation and systemic infection in the adult host, but is less commonly observed in the neonatal small intestine. Instead, here we describe non-professional efferocytosis of Salmonella-infected enterocytes by neighbouring intestinal epithelial cells in the neonatal intestine. Intestinal epithelial stem cell organoid co-cultures of neonatal and adult cell monolayers with damaged enterocytes replicated this observation, confirmed the age-dependent ability of intestinal epithelial cells for efferocytosis and identified the critical involvement of the 'eat-me' signals and adaptors phosphatidylserine and C1q as well as the 'eat-me' receptors integrin-v (CD51) and CD36 in cellular uptake. Consistent with this, massive epithelial cell membrane protrusions and CD36 accumulation at the contact site with apoptotic cells were observed in the infected neonatal host in vivo. Efferocytosis of infected small intestinal enterocytes by neighbouring epithelial cells may represent a previously unrecognised mechanism of neonatal antimicrobial host defense to maintain barrier integrity.