Project description:The epithelial layer of the gastrointestinal tract is the body’s first line of defense against gut pathogens. However, our current understanding of the innate immune response of the epithelial layer is limited. For this study, we used gastrointestinal organoids which have the advantage of being primary, non-transformed epithelium that retains organ-specific characteristics in culture, and also that they lack any confounding immune cells. We systematically profiled the transcriptomes of gastrointestinal epithelial cells using a newly generated biobank of human and murine GI organoids grown from tissue-resident stem cells, providing an atlas of gene expression along the GI tract of both species. RNA sequencing of all lines confirmed the preservation of tissue identity, and in addition revealed extensive organization of innate immune signaling components along the cephalocaudal axis, endowing a specific innate immune profile to each segment.
Project description:In order to test the development of gastrointestinal tract (GIT) in pre-weaned cavles, the GIT tissues were collected from day 0, day 7, day 21 and day 42 calves. RNA-seq was used to measure the transcriptome profiles. The RNA-seq analysis revealed the fast development of small intestine and rumen tissue during the first week after birth.
Project description:The Runx1 transcription factor plays an important role in tissue homeostasis through its effects on stem/progenitor cell populations and differentiation. The effect of Runx1 on epithelial differentiation of the secretory cell lineage of the colon was recently demonstrated. This study aimed to examine the role of Runx1 in tumor development in epithelial cells of the gastrointestinal tract. Conditional knockout mice were generated that lacked Runx1 expression in epithelial cells of the GI tract. These mice were crossed onto the ApcMin background, sacrificed, and their intestinal tumor phenotypes were compared with ApcMin Runx1 wildtype control mice. Apc-wildtype Runx1-mutant mice were also examined for tumor development. Colons from Runx1 knockout and wildtype mice were used for genome-wide mRNA expression analyses followed by gene-specific quantitative RT-PCR of whole colon and colon epithelium, to identify Runx1 target genes. Runx1 deficiency in intestinal epithelial cells significantly enhanced tumorigenesis in ApcMin mice. Notably, epithelial Runx1 deficiency in Apc-wildtype mice was sufficient to cause tumor development. Absence of Runx1 was associated with global changes in expression of genes involved in inflammation and intestinal metabolism, and with gene sets indicative of metastatic phenotype and poor prognosis. Gene-specific analysis of Runx1 deficient colon epithelium revealed increased expression of genes linked to an expansion of the stem/progenitor cell population. These results identify Runx1 as a novel tumor suppressor gene for gastrointestinal tumors and support a role for Runx1 in maintaining the balance between the intestinal stem/progenitor cell population and epithelial differentiation of the GI tract. A total of 8 colon tissue RNA samples were analyzed, comprising 4 colon samples from wild-type mice (Villin-Cre negative / Runx1-floxed) and 4 colon samples from mice that lack epithelial expression of Runx1 (Villin-Cre positive/Runx1-floxed).