Project description:Digestive system development is orchestrated by combinatorial signaling interactions between endoderm and mesoderm, but how they are integrated in the genome is poorly understood. Here we identified the Xenopus foregut and hindgut progenitor transcriptomes, which are largely conserved with mammals. Using RNA-seq and ChIP-seq we show that BMP/Smad1 regulates dorsal-ventral gene expression in both the endoderm and mesoderm, whereas Wnt/b-catenin acts as a genome-wide toggle between foregut and hindgut programs. In addition to b-catenin-Tcf promoting hindgut gene transcription, we unexpectedly observed Wnt-repressed foregut genes associated with b-catenin-binding to DNA lacking Tcf motifs, suggesting a novel direct repression. We define how BMP and Wnt signaling are integrated in the genome with Smad1 and β-catenin co-occupying DNA elements associated with hundreds of key regulatory genes. These results extend our understanding of GI organogenesis and how Wnt and BMP may coordinate genomic responses in other contexts.
2017-02-28 | GSE87652 | GEO
Project description:Glycerol monolaurate alter gut microbiota in yellow feathered broilers
Project description:Digestive system development is orchestrated by combinatorial signaling interactions between endoderm and mesoderm, but how they are integrated in the genome is poorly understood. Here we identified the Xenopus foregut and hindgut progenitor transcriptomes, which are largely conserved with mammals. Using RNA-seq and ChIP-seq we show that BMP/Smad1 regulates dorsal-ventral gene expression in both the endoderm and mesoderm, whereas Wnt/b-catenin acts as a genome-wide toggle between foregut and hindgut programs. In addition to b-catenin-Tcf promoting hindgut gene transcription, we unexpectedly observed Wnt-repressed foregut genes associated with b-catenin-binding to DNA lacking Tcf motifs, suggesting a novel direct repression. We define how BMP and Wnt signaling are integrated in the genome with Smad1 and β-catenin co-occupying DNA elements associated with hundreds of key regulatory genes. These results extend our understanding of GI organogenesis and how Wnt and BMP may coordinate genomic responses in other contexts.
Project description:RNA N6-melthyladenosine has been suggested to play important roles in various biological processes. Chicken ovary development is a process controlled by complex gene regulations. In this study, transcriptome-wide m6A methylation of the Wuhua yellow-feathered chicken ovaries before and after sexual maturation was profiled to identify potential molecular mechanisms underlying chicken ovary development. The results showed that m6A levels of mRNAs changed dramatically during sexual maturity. A total of 1476 differential m6A peaks were found between these two stages with 662 significantly up-regulated methylation peaks and 814 down-regulated methylation peaks after sexual maturation. A positive correlation was found between the m6A peaks and gene expression levels. Functional enrichment analysis indicated that apoptosis related pathways might be the key molecular regulatory pathway underlying the poor reproductive performance of Wuhua yellow-feathered chicken. The fine expressional regulation of genes related to follicles development and follicle atresia controlled by m6A during the maturity results in the poor reproductive performance in the Wuhua yellow-feathered chicken. However, the regulatory mechanisms are still unclear, thus more further studies are required. The pathways and corresponding candidate genes found here may be useful for molecular design breeding for improving egg production performance in Chinese local chicken breed, and it will also benefit for the genetic resource protection of valuable avian species.
Project description:Esophageal adenocarcinoma (EA) is increasingly common. EA is thought to arise from a precursor lesion, Barrett’s esophagus (BE), in which chronic bile and acid reflux from the stomach injures the esophagus and induces the esophageal squamous epithelium to transition to a mixed gastric and intestinal glandular mucosa. The molecular determinants driving this metaplasia are poorly understood. We established a biobank of human patient-derived BE organoids that recapitulated the molecular heterogeneity of BE. Bulk and single-cell transcriptomics, corroborated with analysis of patient tissues, pointed to BE differentiation depending on a balance between two transcription factors that govern foregut versus hindgut embryonic gastrointestinal development: SOX2 (driving esophageal and stomach differentiation) and CDX2 (driving intestinal differentiation). Using squamous-specific inducible Sox2 knockout (Krt5CreER/+; Sox2Δ/Δ;ROSA26LSLTdTomato/+) mice, we found increased basal proliferation and decreased differentiation in the foregut squamous epithelium. Remarkably, Sox2Δ/Δ mice also harbored expanded glands at the squamocolumnar junction, some of which lineage traced to Krt5-expressing cells, indicating metaplasia from squamous epithelium. CUT&RUN analysis showed SOX2 bound and promoted differentiation-associated (e.g.,Krt13) and repressed proliferation-associated (e.g., Mki67) targets. Thus, SOX2 is critical for foregut squamous epithelial differentiation and its decreased expression likely an initiating step in progression to BE and thence to EA.
Project description:Interorgan signaling events are emerging as key regulators of behavioral plasticity. The foregut and hindgut circuits of the C. elegans enteric nervous system (ENS) control feeding and defecation behavior, respectively. Here we show that epithelial cells in the midgut integrate feeding state information to control these behavioral outputs via releasing distinct neuropeptidergic signals. In favorable conditions, insulin and non-insulin peptides released from midgut epithelia activate foregut and hindgut enteric neurons, respectively, to sustain normal feeding and defecation behavior. During food scarcity, altered insulin signaling from sensory neurons activates the transcription factor DAF-16/FoxO in midgut epithelia, which blocks both peptidergic signaling axes to the ENS via transcriptionally shutting down the intestinal neuropeptide secretion machinery. Our findings demonstrate that midgut epithelial cells act as integrators to relay internal state information to distinct parts of the enteric nervous system to control animal behavior.
Project description:Age-matched stage 13 embryos were dissected and cDNA of 8 organs from each embryo were sequenced. The organs were foregut, anterior midgut, posterior midgut, hindgut, Malpighian tubules, left salivary gland, right salivary gland, ventral nerve cord. Gene expression, transcription start and stop sites, and strands of termini were analysed. SMART amplification adapters were used for finding transcript termini and for phasing.
2017-02-01 | GSE77429 | GEO
Project description:Effects of dietary trehalose supplementation on intestinal flora of yellow-feathered broilers under heat stress