BMP gradient along the intestinal villus axis controls zonated enterocyte and goblet cell states
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA798725 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Single cell and bulk RNA sequencing was performed from human intestinal organoids differentiated for 5 days in the presence or absence of BMP-2 and BMP-4 ligands.
2022-05-02 | GSE194004 | GEO
Project description:The intestinal epithelium is a highly structured tissue composed of repeating crypt-villus units. Enterocytes, which constitute the most abundant cell type, perform the diverse tasks of absorbing a wide range of nutrients while protecting the body from the harsh bacterial-rich environment. It is unknown if these tasks are equally performed by all enterocytes or whether they are spatially zonated along the villus axis. Here, we performed whole-transcriptome measurements of laser-capture-microdissected villus segments to extract a large panel of landmark genes, expressed in a zonated manner. We used these genes to localize single sequenced enterocytes along the villus axis, thus reconstructing a global spatial expression map. We found that most enterocyte genes were zonated. Enterocytes at villi bottoms expressed an anti-bacterial Reg gene program in a microbiome-dependent manner, potentially reducing the crypt pathogen exposure. Translation, splicing and respiration genes steadily decreased in expression towards the villi tops, whereas distinct mid-top villus zones sub-specialized in the absorption of carbohydrates, peptides and fat. Enterocytes at the villi tips exhibited a unique gene-expression signature consisting of Klf4, Egfr, Neat1, Malat1, cell adhesion and purine metabolism genes. Our study exposes broad spatial heterogeneity of enterocytes, which could be important for achieving their diverse tasks.
2018-02-07 | GSE109413 | GEO
Project description:We analyzed gene expression profiles in isolated mouse LGR5+ intestinal stem cells, lineage-specific enterocyte and secretory progenitors, and terminally differentiated villus enterocytes. Gene Ontology analyses of cell type-specific transcripts indicated their expected biological functions. We hybridized Affmetrix 430A 2.0 mouse microarrays with processed RNA isolated from purified Lgr5+ intestinal stem cells, secretory (Sec-Pro) and enterocyte (Ent-Pro) crypt progenitors, and mature villus enterocytes (ENT).
2014-01-06 | E-GEOD-51398 | biostudies-arrayexpress
Project description:We analyzed gene expression profiles in isolated mouse LGR5+ intestinal stem cells, lineage-specific enterocyte and secretory progenitors, and terminally differentiated villus enterocytes. Gene Ontology analyses of cell type-specific transcripts indicated their expected biological functions.
2014-01-06 | GSE51398 | GEO
Project description:Enteroendocrine cells (EECs) control a wide range of physiological processes linked to metabolism1. We show that EEC hormones are differentially expressed between crypts (for example, Glp1) and villi (for example, secretin). As demonstrated by single-cell mRNA sequencing using murine Lgr5+ cell-derived organoids, BMP4 signals alter the hormone expression profiles of individual EECs to resemble those found in the villus. Accordingly, BMP4 induces hormone switching of EECs migrating up the crypt-villus axis in vivo. Our findings imply that EEC lineages in the small intestine exhibit a more flexible hormone repertoire than previously proposed. We also describe a protocol to generate human EECs in organoids and demonstrate a similar regulation of hormone expression by BMP signalling. These findings establish alternative strategies to target EECs with therapeutically relevant hormone production through BMP modulation.
| S-EPMC6276989 | biostudies-literature
Project description:Krüppel-like factor 9 (Klf9), a zinc-finger transcription factor, is implicated in the control of cell proliferation, cell differentiation and cell fate in brain and uterus. Using Klf9 null mutant mice, we have investigated the involvement of Klf9 in small intestine crypt-villus cell renewal and lineage determination. We report the predominant expression of Klf9 gene in small intestine smooth muscle (muscularis externa). Jejunums null for Klf9 have shorter villi, reduced crypt stem/transit cell proliferation, and altered lineage determination as indicated by decreased and increased numbers of Goblet and Paneth cells, respectively. A stimulatory role for Klf9 in villus cell migration was demonstrated by BrdU labeling. Results suggest that Klf9 controls the elaboration, from small intestine smooth muscle, of molecular mediator(s) of crypt cell proliferation and lineage determination, and of villus cell migration. Keywords: Genetic modification
2006-12-08 | GSE6443 | GEO
Project description:High numbers of goblet cells in airways contribute to the mucus obstruction characteristic of asthmatic airways. Allergen challenged mice exhibit robust expression of goblet cells within airway surface epithelium. This study looks at the temporal analysis of IL-13 exposed murine airways to elucidate pathways that result in differentiation of airway epithelial cells to goblet cells.
2008-06-13 | E-GEOD-481 | biostudies-arrayexpress
Project description:High numbers of goblet cells in airways contribute to the mucus obstruction characteristic of asthmatic airways. Allergen challenged mice exhibit robust expression of goblet cells within airway surface epithelium. This study looks at the temporal analysis of IL-13 exposed murine airways to elucidate pathways that result in differentiation of airway epithelial cells to goblet cells. Keywords: other
2003-07-16 | GSE481 | GEO
Project description:Understanding the mechanisms involved in colonic epithelial differentiation is key to unraveling the alterations causing inflammatory conditions and cancer. Organoid cultures provide a unique tool to address these questions but studies are scarce. We report a differentiation system toward enterocytes and goblet cells, the two major colonic epithelial cell lineages, using organoids from human healthy tissue. Culture of normal patient-derived colon organoids in medium lacking stemness agents resulted in a modest ultrastructural differentiation phenotype with low-level expression of enterocyte (KLF4, KRT20, CA1) and goblet cell (TFF2, TFF3, AGR2) lineage markers. BMP pathway activation through depletion of Noggin and addition of BMP4 resulted in enterocyte-biased differentiation. Contrarily, blockade of the Notch pathway using the g-secretase inhibitor dibenzazepine (DBZ) favored goblet cell differentiation. Combination treatment with BMP4 and DBZ caused a balanced strong induction of both lineages. In contrast, colon tumor organoids responded poorly to BMP4 and DBZ showing only weak signals of cell differentiation. We also investigated the effects of 1α,25-dihydroxyvitamin D3 (calcitriol) on differentiation. Calcitriol attenuated the effects of the BMP4 and DBZ on normal colon organoids, with reduced expression of differentiation genes and phenotype. Consistently, in normal organoids, calcitriol inhibited early signaling by BMP4 as assessed by reduction of the level of phospho-SMAD1/5/8. Our results show that BMP and Notch signaling play key roles in human colon stem cell differentiation to the enterocytic and goblet cell lineages and that calcitriol modulates these processes favoring stemness features.
2024-04-15 | GSE248274 | GEO
Project description:A cell’s proteome is an important determinant of its functional state, however the use of transcriptomes as reliable proxies for cellular proteomes is debatable. In the small intestine, nutrient absorbing enterocytes operate for four days as they migrate along villi, highly graded microenvironments. Spatial transcriptomics demonstrated profound zonation in enterocyte gene expression, but how this variability translates to protein content is unclear. Here, we used spatial sorting to generate global spatial maps of enterocyte proteins and mRNAs along the villus axis. We found that both were zonated, yet often spatially anti-correlated. We developed a Bayesian approach to infer protein translation and degradation rates from the combined spatial profiles, and demonstrate that space-independent protein-synthesis delays can explain the mRNA-protein discordances. Our work provides a proteomic spatial blueprint of the intestinal epithelium and highlights the importance of protein measurements for inferring states of tissue cells that operate outside of steady state.
2021-10-09 | GSE164746 | GEO