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:Organs are not uniform; distinct transcriptional and metabolic territories are apparent in key metabolic organs such as the intestine, liver or pancreas. Whether and why such organ zonation differs between the sexes remains to be explored, despite increasing interest in documenting and functionally interrogating sex differences in physiology. Here, we use the intestine of adult Drosophila to explore mechanisms of adult organ zonation. Through metabolic profiling, we uncover sex and regional differences in intestinal lipid metabolism. Cell type- and adult-specific genetic manipulations reveal a role for the Myc transcription factor in establishing sex-biased and regional intestinal lipid profiles. myc is repressed in male enterocytes by the sex determinant Doublesex, rendering Myc expression female-biased. Genetic gain- and loss-of-function experiments indicate that this Dsx-Myc antagonism in enterocytes underlies the sexually dimorphic and regional intestinal lipid profiles. The actions of Myc in gut enterocytes are physiologically significant: they extrinsically sustain female-biased lipid storage and fecundity. Our findings establish Myc as a new member of the sex differentiation pathway and a key regulator of organ zonation. They also underscore the need to consider the intestine as a previously unrecognised contributor to widely documented sex differences in lipid metabolism.
Project description:Organs exhibit distinct transcriptional and metabolic territories; how and why such organ zonation differs between the sexes is unclear. Using adult Drosophila intestines, we combine whole-organ 3D cellular mapping with metabolic profiling to uncover regional differences in enterocyte size and metabolism that vary by sex and genotype. Zonation arises from opposing, region-specific and sex-biased actions of the sex determinant Doublesex (Dsx) and the transcription factor Myc. In enterocytes, male-specific Dsx suppresses Myc, rendering its expression female-biased. Dsx–Myc antagonism enlarges female enterocytes, increasing their ploidy in specific gut regions. It also drives a female-specific lipid profile, marked by sex-biased expression of a cluster of lipases and selective triacylglycerol storage in the anterior midgut. Myc activity in female enterocytes sustains peripheral lipid reserves and fecundity. These findings identify relevant roles for Myc in sex differentiation and the intestine as a key, previously overlooked contributor to sex differences in lipid metabolism.
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:The intestinal epithelium undergoes robust maturation postnatally, yet its early-life characteristics remain poorly understood. Using single-cell RNA sequencing, we analyzed intestinal epithelial cells from neonatal (10-day-old) and juvenile (21-day-old) mice reared under both specific pathogen-free and germ-free conditions. Among the various cell types comprising the intestinal epithelia, we found that enterocytes, in particular, exhibit markedly different features between these stages. Enterocytes of neonatal mice show reduced expression of secretory host defense-related genes independently of microbial colonization. These genes are upregulated in juvenile enterocytes in a microbiota-dependent manner. Conversely, neonatal enterocytes display upregulation of ketogenesis-related genes, which correlates with high expression of genes contributing to cell morphogenesis rather than serving primarily as an energy source. These findings provide novel insights into early-life maturation of intestinal epithelia offering implications for understanding neonatal intestinal pathologies.