Dissection of gastric homeostasis in vivo facilitates permenant capture of isthmus stem cells in vitro [Lgr5, Sox2]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA899077 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22220800_1.fastq.gz | Fastqsanger.gz | |||
| SRR22220800_2.fastq.gz | Fastqsanger.gz | |||
| SRR22220801_1.fastq.gz | Fastqsanger.gz | |||
| SRR22220801_2.fastq.gz | Fastqsanger.gz | |||
| SRR22220802_1.fastq.gz | Fastqsanger.gz |
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Project description:The glandular stomach is comprised of two regenerative compartments termed corpus and antrum, yet our understanding of the cell populations that maintain these epithelia is incomplete. Here, we show that cell types with equivalent functional roles in the corpus and antrum share similar transcriptional states including the immature isthmus population. To study isthmus cells, we developed a monolayer (2D) culture that is continually maintained via Lgr5-negative cells and produces diverse gastric cell types. Importantly, 2D cultures can be interconverted into conventional 3D organoids, recapitulating the plasticity of gastric epithelial cells in vivo. Finally, we utilized the 2D culture system to show that rare Sox2-expressing cells resemble enterochromaffin (EC) cells and Sox2 is both necessary and sufficient to generate EC cells. Together, our data provide important insights into the basis of gastric homeostasis, establish a tractable culture system to capture isthmus cells and uncover a role for Sox2 in EC cells.
2022-11-10 | GSE217471 | GEO
Project description:The glandular stomach is comprised of two regenerative compartments termed corpus and antrum, yet our understanding of the cell populations that maintain these epithelia is incomplete. Here, we show that cell types with equivalent functional roles in the corpus and antrum share similar transcriptional states including the immature isthmus population. To study isthmus cells, we developed a monolayer (2D) culture that is continually maintained via Lgr5-negative cells and produces diverse gastric cell types. Importantly, 2D cultures can be interconverted into conventional 3D organoids, recapitulating the plasticity of gastric epithelial cells in vivo. Finally, we utilized the 2D culture system to show that rare Sox2-expressing cells resemble enterochromaffin (EC) cells and Sox2 is both necessary and sufficient to generate EC cells. Together, our data provide important insights into the basis of gastric homeostasis, establish a tractable culture system to capture isthmus cells and uncover a role for Sox2 in EC cells.
2022-11-10 | GSE217470 | GEO
Project description:The glandular stomach is comprised of two anatomically and functionally distinct epithelial tissues termed corpus and antrum. While these compartments continuously regenerate to ensure normal organ function, our understanding of the molecular and cellular determinants that maintain these tissues remains incomplete. Here, we established an unbiased account of all gastric epithelial cells of the mouse corpus and antrum using single cell RNA-sequencing, allowing us to compare these adjacent epithelia and their stem cell compartments. Our data reveals that epithelial cell types with equivalent functional roles in the corpus and antrum utilize similar transcriptional programs, and our results support the existence of two discernible stem cell populations within the gland base and isthmus regions of these tissues. To study isthmus stem cells, typically underrepresented in conventional, gland base-enriched organoid cultures, we developed a novel 2D monolayer culture system to propagate mouse and human gastric epithelia. These 2D cultures expand indefinitely via Lgr5- isthmus-like cells and maintain the ability to differentiate into diverse gastric cell types. While 2D corpus and antrum cultures were transcriptionally similar, they retained a molecular memory and differentiation bias that mirrored their tissue of origin. Furthermore, gastric 2D cultures could be readily and reversibly converted into conventional 3D organoids, highlighting the remarkable plasticity of undifferentiated stomach epithelial cells. Finally, we utilized the 2D culture system to show that rare primary epithelial cells with high levels of Sox2 expression, previously hypothesized to be gastric stem cells, most closely resembled enterochromaffin (EC) cells and Sox2 is both necessary and sufficient to generate EC cells in vivo. Together, our data (i) provide important insights into the basis of gastric epithelial regeneration and differentiation, (ii) establish a tractable 2D culture system to capture and manipulate primary gastric isthmus stem cells in vitro and (iii) uncover a role for the stem cell factor Sox2 during EC cell specification.
2022-11-10 | GSE217472 | GEO
Project description:Dissection of gastric homeostasis in vivo facilitates permenant capture of isthmus stem cells in vitro
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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.
2019-03-25 | GSE124930 | GEO
Project description:Dissection of gastric homeostasis in vivo facilitates permenant capture of isthmus stem cells in vitro [2D culture]
| PRJNA899078 | ENA
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.
2019-01-01 | GSE108729 | GEO
Project description:Dissection of gastric homeostasis in vivo facilitates permanent capture of isthmus stem cells in vitro [single-cell RNA-seq]
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Project description:The currently accepted intestinal epithelial cell organization model equates crypt base columnar (CBC) cells, marked by high levels of Lgr5 expression, with the intestinal stem cell (ISC). However, recent intestinal regeneration studies have uncovered limitations of the ‘Lgr5-CBC’ model, leading to two major views: one favoring the presence of a quiescent reserve stem cell population, the other calling for differentiated cell plasticity. To test if an alternative model may help reconcile these perspectives, we studied the hierarchical organization of crypt epithelial cells in an unbiased fashion, by combining high-resolution, single-cell profiling and lineage tracing in multiple transgenic mouse models. These show that Lgr5 is not a specific ISC marker; rather, cells located in the crypt isthmus, which include Lgr5low cells, comprise the ISCs that sustain tissue homeostasis. Following irradiation or intestinal injury, surviving ISCs and progenitors, but not differentiated cells, participate in intestinal regeneration, suggesting that neither de-differentiation nor reserve stem cell populations are drivers of intestinal regeneration. Our results provide a novel viewpoint for the intestinal crypt epithelium, in which ISCs localize to the crypt isthmus, and ISC potential is restricted to stem and progenitor cells.
2024-03-24 | GSE205229 | GEO
Project description:Wnt signaling stimulated by R-spondin (Rspo) via binding to Lgr family members is crucial for stem cell renewal and tissue homeostasis in the gastrointestinal tract. In the stomach, Rspo is secreted by myofibroblasts and controls epithelial gland regeneration by inducing proliferation of Wnt-responsive Axin2+ cells in the isthmus of glands. Infection with Helicobacter pylori results in increased expression of stromal Rspo, leading to an expansion of Axin2+ isthmus stem cells and gland hyperplasia. Basal Lgr5+ cells are exposed to Rspo3 but the effects of this are not well understood. Here we demonstrate that, in the antrum, endogenous Rspo3, apart from its activity as a mitogen, regulates Lgr5+ cells in the gland base and induces their differentiation towards secretory cells.
2019-04-02 | GSE129107 | GEO