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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

Intestinal BMP SMADs impart the mid-villus pattern via direct targeting of villus zonation genes and by controlling a transcription factor hierarchy [Spatial Transcriptomics]

Project description:Intestinal villus enterocytes exist in spatially restricted cell states, called zones, and continuously transdifferentiate as they migrate toward the villus tip. Bone morphogenetic protein (BMP) signaling through the BMPR1A receptor is required for zonation of enterocytes; however, the molecular mechanisms and transcriptional regulators downstream of BMP ligands/receptors are unclear. Using compound genetic mouse models and epigenomic techniques, we find that SMAD1 and SMAD5 are necessary for activation of middle villus zone genes via direct binding and control of a transcription factor hierarchy. Spatial transcriptomics reveal a homeotic-like shift in the villus pattern of SMAD1/SMAD5 double mutants, with the villus bottom and tip domains expanding at the expense of the middle. Surprisingly, SMAD1 and SMAD5 are not required for regulation of villus tip identity, which is dependent on SMAD4. Epigenomics approaches identify a mechanism for villus patterning in which SMAD1/5 directly activate some mid-villus genes and control others via a transcription factor hierarchy, including a SMAD-regulated transcription factor, TBX3, as a downstream effector of villus zonation.

2026-08-05 | GSE313353 | GEO

Intestinal BMP SMADs impart the mid-villus pattern via direct targeting of villus zonation genes and by controlling a transcription factor hierarchy [ATAC-seq]

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Intestinal BMP SMADs impart the mid-villus pattern via direct targeting of villus zonation genes and by controlling a transcription factor hierarchy [RNA-seq]

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Intestinal BMP SMADs impart the mid-villus pattern via direct targeting of villus zonation genes and by controlling a transcription factor hierarchy [CUT&Run]

2026-08-05 | GSE313354 | 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

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Intestinal BMP SMADs impart the mid-villus pattern via direct targeting of villus zonation genes and by controlling a transcription factor hierarchy [ATAC-seq]

Project description:Intestinal BMP SMADs impart the mid-villus pattern via direct targeting of villus zonation genes and by controlling a transcription factor hierarchy [ATAC-seq]

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Intestinal BMP SMADs impart the mid-villus pattern via direct targeting of villus zonation genes and by controlling a transcription factor hierarchy [Spatial Transcriptomics]

Project description:Intestinal BMP SMADs impart the mid-villus pattern via direct targeting of villus zonation genes and by controlling a transcription factor hierarchy [Spatial Transcriptomics]

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