Expression data from P14 Lgr5-2A-EGFP mouse uterus
Ontology highlight
ABSTRACT: Epithelial gland development within the uterine lining during prepubertal period is important to ensure successful gestation in adults. Lgr5 expression in uterus becomes largely restricted to the tips of developing glands after birth. These Lgr5 highly expressing cells function as stem cells during gland development. We used microarrays to detail the gene expression profilings and compare between Lgr5 highly and negatively expressing cells in developing uterus.
Project description:Lgr5 is a novel marker expressing in the interzone from around e14.5 of developing synovial joint. By comparing the expression profiles of e14.5 Lgr5+ interzone cells, surrounding Lgr5- non-interzone cells and also e13.5 digit, we have identified some differential expressing genes in the interzone. We have generated bulk RNAseq data of e14.5 Lgr5+ interzone cells, surrounding non-interzone cells and e13.5 Sox9+ chondrocytes cells in digit.
Project description:Forkhead box A2 (FOXA2) is a critical regulator of endometrial gland development in mice. In the adult mouse uterus, FOXA2 is expressed solely in the GE cells of the endometrium. Conditional deletion of Foxa2 after birth in the uterus, using the progesterone receptor Cre mouse (PgrCre), impeded gland development, thereby rendering the adult mouse infertile due to defects in blastocyst implantation stemming from a lack of endometrial glands and their secretions. As a first step to begin understanding the FOXA2 function in the endometrial glands of the uterus, genome-wide investigation of in vivo FOXA2 and RNA polymerase II (POL2) binding target regions in the neonatal and adult uterus was determined by chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-Seq). In order to determine the transcriptional regulatory networks mediating FOXA2 regulation of endometrial gland development and function, chromatin immunoprecipitation and massively parallel sequencing (ChIP-Seq) was used to create a genome-wide profile of in vivo FOXA2-binding sites in the developing (PD 12) and adult (DOPP 2.5 and 3.5) mouse uterus.
Project description:R-spondin (Rspo) signaling is crucial for stem cell renewal and tissue homeostasis in the gastrointestinal tract. In the stomach, Rspo is secreted from myofibroblasts and controls epithelial gland regeneration by inducing proliferation of Wnt-responsive Axin2+ cells in the isthmus of the gland. Infection with H. pylori results in increased expression of stromal Rspo, leading to an expansion of Axin2+ isthmus stem cells and gland hyperplasia. Lgr5+ cells in the gland base are exposed to Rspo3 but the effects of this are not well understood. Here we demonstrate that apart from its activity as a mitogen, endogenous Rspo3 regulates gene expression of Lgr5+ cells in the gastric gland base. Surprisingly, Rspo3 induces differentiation within the Lgr5+ compartment towards secretory deep mucous cells. Moreover, the Rspo3-Lgr5 axis turns out to be a stimulus of epithelial antimicrobial defense. Infection with H. pylori induces a strong antimicrobial response, with Lgr5+ cells expressing antimicrobial compounds that are secreted into the lumen in an Rspo3-dependent manner. Depletion of Lgr5+ cells or knockout of Rspo3 in myofibroblasts leads to hyper-colonization of gastric glands, including the stem cell compartment, whereas systemic application of recombinant Rspo clears H. pylori from the glands. We provide an intriguing, unexpected feature of the Rspo3-Lgr5 axis in the stomach, exhibiting antimicrobial self-protection of the gland to protect the stem cell compartment from invading pathogens.
Project description:The existence and function of Lgr5+ cells within the developing esophagus remains unknown. Here, we document multiple discrete Lgr5+ populations in the developing mouse esophagus, predominantly within nascent epithelial and external muscle layers. Lgr5 expression initially emerges in the developing proximal embryonic epithelium, but progressively extends distally and persists within the distal epithelium of neonates. Fate mapping and ablation analyses reveal a long-term contribution of epithelial Lgr5+ cells to esophageal organogenesis. Additionally, Lgr5-expressing cells are present in the developing external muscle layer, particularly during the development of the striated component. Fate mapping reveals a significant contribution of these embryonic Lgr5+ cells to the adult muscle layer. Embryonic Lgr5+ epithelial cells are also found to be important for regulating epithelial development, serving as a key source of Wnt6, among other ligands, to promote epithelial cell proliferation and formation of epithelial layers. These findings significantly enhance our understanding of esophageal development and shed light on the involvement of Lgr5+ stem/progenitor cells during organogenesis. Importantly, this study lays the foundation for investigating esophageal diseases related to the Lgr5+ stem/progenitor cell pool.
Project description:The existence and function of Lgr5+ cells within the developing esophagus remains unknown. Here, we document multiple discrete Lgr5+ populations in the developing mouse esophagus, predominantly within nascent epithelial and external muscle layers. Lgr5 expression initially emerges in the developing proximal embryonic epithelium, but progressively extends distally and persists within the distal epithelium of neonates. Fate mapping and ablation analyses reveal a long-term contribution of epithelial Lgr5+ cells to esophageal organogenesis. Additionally, Lgr5-expressing cells are present in the developing external muscle layer, particularly during the development of the striated component. Fate mapping reveals a significant contribution of these embryonic Lgr5+ cells to the adult muscle layer. Embryonic Lgr5+ epithelial cells are also found to be important for regulating epithelial development, serving as a key source of Wnt6, among other ligands, to promote epithelial cell proliferation and formation of epithelial layers. These findings significantly enhance our understanding of esophageal development and shed light on the involvement of Lgr5+ stem/progenitor cells during organogenesis. Importantly, this study lays the foundation for investigating esophageal diseases related to the Lgr5+ stem/progenitor cell pool.
Project description:R-spondin (Rspo) signaling is crucial for stem cell renewal and tissue homeostasis in the gastrointestinal tract. In the stomach, Rspo is secreted from myofibroblasts and controls epithelial gland regeneration by inducing proliferation of Wnt-responsive Axin2+ cells. Infection with H. pylori results in increased expression of stromal Rspo, leading to an expansion of Axin2+ isthmus stem cells and gland hyperplasia. Lgr5+ stem cells are exposed to Rspo3 but the effects of this are not well understood. Here we demonstrate that in addition to its effect as a mitogen, endogenous Rspo3 regulates the gene expression of Lgr5+ cells in the gland base in both antrum and corpus. Rspo3 inhibits proliferation and induces differentiation within the Lgr5+ compartment towards a secretory phenotype. Strikingly, the Rspo3-Lgr5 axis turns out to be required for epithelial antimicrobial defense. Infection with H. pylori induces a strong antimicrobial response, with Lgr5+ cells expressing antimicrobial compounds that are secreted into the lumen in an Rspo3-dependent manner. Depletion of Lgr5+ cells or knockout of Rspo3 in myofibroblasts leads to dramatic hyper-colonization of gastric glands, including the stem cell compartment, whereas systemic application of recombinant Rspo is sufficient to clear H. pylori from the glands. We provide an intriguing, unexpected feature of Lgr5+ cells, exhibiting an indivisible connection between stem cell signaling and antimicrobial self-protection.
Project description:This study identifies a novel role for the Hoxc9,10,11 genes in uterine gland formation. This function is redundant with the Hoxa9,10,11 and Hoxd9,10,11 genes and is only seen in a sensitized genotype with reduced expression of these paralogs. We further used scRNA-seq to define the gene expression patterns of the multiple cell types of the developing uterus. The results define the gene expression patterns driving lineage specific development. In addition scRNA-seq was used to characterize the perturbed gene expression levels of all developing uterus cell types in the ACD+/- and ACD+/-WTA11 mutants. Particularly striking was the reduced Wnt signaling and the disruption of the Cxcl12/Cxcr4 axis in the mutants.