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The crosstalk between BMP and Wnt signaling establishes the equilibrium of villus length in mammalian small intestine

ABSTRACT: The crosstalk between BMP and Wnt signaling establishes the equilibrium of villus length in mammalian small intestine

PROVIDER: PRJNA1036121 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26678469_1.fastq.gz	Fastqsanger.gz
	SRR26678469_2.fastq.gz	Fastqsanger.gz
	SRR26678470_1.fastq.gz	Fastqsanger.gz
	SRR26678470_2.fastq.gz	Fastqsanger.gz
	SRR26678471_1.fastq.gz	Fastqsanger.gz

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The crosstalk between BMP and Wnt signaling establishes the equilibrium of villus length in mammalian small intestine

Project description:The precise regulatory mechanisms governing the quantitative balance of epithelial cells in the small intestine have long remained elusive. In this study, we reveal a gradual strengthening of BMP signaling from the proximal to distal segments. Through the utilization of genetically engineered mice, we demonstrate that BMP signaling plays a pivotal role in governing villus length. Furthermore, employing mathematical modeling, we uncover that BMP signaling acts as a cellular positional information sensor, orchestrating cell apoptosis and inhibiting cell proliferation. This collective regulation of cellular processes leads to the observed disparities in villus length between the proximal and distal segments of the small intestine. Notably, BMP signaling inhibits Wnt signaling to control the rate of villus growth, while Wnt signaling reciprocally upregulates BMP to maintain villus length under conditions of excessive proliferation. The spatial crosstalk between BMP and Wnt signaling networks collectively ensures the homeostasis of villus length. Our comprehensive investigation of the key factors underlying the gradient differences in villus length provides crucial insights for a deeper understanding of the functional dynamics of the small intestine.

2025-04-28 | GSE247044 | GEO

Terminal differentiation of villus-tip enterocytes is governed by distinct members of Tgfb superfamily

Project description:The protective and absorptive functions of the intestinal epithelium rely on differentiated enterocytes in the villi. The differentiation of enterocytes is orchestrated by sub-epithelial mesenchymal cells producing distinct ligands along the villus axis, in particular Bmps and Tgf. Here we show that individual Bmp ligands and Tgf drive distinct enterocytic programs specific to villus zonation. Bmp4 is expressed mainly from the centre to the upper part of the villus, and it activates preferentially genes connected to lipid uptake and metabolism. In contrast, Bmp2 is produced by villus-tip mesenchymal cells, and it influences the adhesive properties of villus-tip epithelial cells and the expression of antimicrobial peptides. Hence, Bmp2 promotes the terminal enterocytic differentiation at the villus-tip. Additionally, Tgf induces an epithelial gene expression programs similar to that triggered by Bmp2. The inhibition of Bmp receptor type I in vivo and using intestinal organoids lacking Smad4 revealed that Bmp2-driven villus-tip program is activated by a canonical Smad-dependent mechanism. Finally, we established an organoid cultivation system that enriches for villus-tip enterocytes and thereby better mimics the cellular composition of the intestinal epithelium. Altogether our data suggest that not only Bmp gradient, but also the activity of individual Bmp drives specific enterocytic programs.

2023-07-01 | GSE216699 | GEO

BMP gradient along the intestinal villus axis controls zonated enterocyte and goblet cell states

Project description:BMP gradient along the intestinal villus axis controls zonated enterocyte and goblet cell states

| PRJNA798725 | ENA

BMP gradient along the intestinal villus axis controls zonated enterocyte and goblet cell states

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

Asymmetric crosstalk between the BMP and TGFb pathways resolves signaling ambiguity

Project description:The BMP and TGFβ signaling pathways control cellular fate decisions in diverse biological contexts, often playing opposing roles. Despite extensive knowledge of these pathways, understanding how cells respond to environments containing these opposing cues remains a challenge. Here, we systematically analyze the activation of BMP and TGFβ pathways under combinatorial signaling environments. We find that TGFβ ligands inhibit BMP signaling, while BMP ligands enhance TGFβ transcriptional response, across concentrations, ligand variants, and cell types. This asymmetric crosstalk results in the activation of a single specific transcriptional response, even under mixed signaling conditions, effectively reducing signal ambiguity. Furthermore, we show that this crosstalk originates downstream of the SMAD proteins phosphorylation. Using mathematical models we predict, and experimentally verify, that promiscuous interactions between SMAD proteins provide the mechanism for the observed crosstalk. Our findings challenge the canonical models of signaling pathways, suggesting an active role for mediator proteins in determining biological responses.

2024-12-30 | GSE254418 | GEO

Crosstalk with astrocytes establishes tumor edge in glioblastoma

Project description:Crosstalk with astrocytes establishes tumor edge in glioblastoma

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Gene expressional change along crypt-villus in rats jejunum

Project description:Transcriptional profiling of jejunal gene expression during the differentiation from crypt to villus cells in rats, using cryostat sections of the villus-crypt columns.

2009-04-05 | GSE15421 | GEO

Lysolecithin as feed additive enhances collagen expression and villus length in the jejunum of broiler chickens

Project description:Adding lysolecithin to feed has reportedly improved the performance of broiler chickens. Lysolecithin is generated by phospholipase catalyzed hydrolysis of lecithin. The enzymatic reaction converts phospholipids into lysophospholipids, with lysophosphatidylcholine (LPC) the primary product. Here we compared supplementation with a commercial lysolecithin (Lysoforte(R) Kemin Industries, Inc., Des Moines, IA) with comparable levels of purified LPC for effects on broilers. Despite no differences in weight gain during the starter period, we discovered a significant increase in average villus length in the jejunum with lysolecithin, but not with LPC. High-throughput gene expression microarray analyses revealed many more genes were regulated in the epithelium of jejunum by lysolecithin compared to LPC. The most upregulated genes and pathways were for collagen, extracellular matrix and integrins. Staining sections of jejunum with Sirius Red confirmed the increased deposition of collagen fibrils in villi of broilers fed lysolecithin but not LPC. Thus, lysolecithin elicits gene expression in the intestinal epithelium leading to enhanced collagen deposition and villus length. LPC alone as a supplement does not mimic these responses. Feed supplementation with lysolecithin triggers changes in the intestinal epithelium with the potential to improve overall gut health and performance.

2019-02-01 | GSE94622 | GEO

Mindbomb1 is a Novel Negative Regulator of BMP Signaling

Project description:Mindbomb1 is a Novel Negative Regulator of BMP Signaling.

2024-07-02 | MSV000095215 | MassIVE

Gene regulatory networks along the small intestinal crypt-villus axis

Project description:Genes encoding transcription factors function as hubs in gene regulatory networks because they encode DNA-binding proteins, which bind to promoters that carry their binding sites. In the present work we have studied gene regulatory networks defined by genes with transcripts belonging to different mRNA abundance classes in the small intestinal epithelial cell. The focus is the rewiring that occurs in transcription factor hubs in these networks during the differentiation of the small intestinal epithelial cell while it migrates along the crypt-villus axis and during its development from a fetal endodermal cell to a mature adult villus epithelial cell. We have generated transcriptome data for mouse small intestinal villus, crypt and fetal intestinal epithelial cells. In addition we have generated metabolome data from crypt and villus cells. Our results show that the intestinal crypt transcription factor hubs that are rewired during differentiation are involved in the cell cycle process (E2F, NF-Y) and stem cell maintenance (c-Myc). In contrast the villi are dominated by a HNF-4 villus hub, which is rewired during differentiation by the addition of network genes with relevance for lipoprotein synthesis and lipid absorption. Moreover, we have identified a villus NF-kB hub, which was revealed by comparison of the villus and endoderm transcriptomes. The rewiring of the NF-kB villus hub during intestinal development reflects transcriptional activity established by host and microflora interactions. To aid in the mining of our results we have developed a web portal (http://gastro.imbg.ku.dk/mousecv/) allowing easy linkage between the transcriptomic data, biological processes and functions. Keywords: Cell type comparison

2005-11-29 | GSE3216 | GEO

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