Evidence that inflammation-associated fibroblasts (IAFs) originate from Edil3 stromal "mesitocytes" in the colon following radiation injury
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE268790 | GEO | 2024/06/01
REPOSITORIES: GEO
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Project description:Signals from the surrounding niche drive proliferation and suppress differentiation of intestinal stem cells (ISCs) at the bottom of intestinal crypts. Among sub-epithelial support cells, deep sub-cryptal CD81+ PDGFRAlo trophocytes capably sustain ISC functions ex vivo. Here we show that mRNA and chromatin profiles of abundant CD81- PDGFRAlo mouse stromal cells resemble those of trophocytes and that both populations provide crucial canonical Wnt ligands. Mesenchymal expression of key ISC-supportive factors extends along a spatial and molecular continuum from trophocytes into peri-cryptal CD81- CD55hi cells, which mimic trophocyte activity in organoid co-cultures. Graded expression of essential niche factors is not cell-autonomous but dictated by the distance from bone morphogenetic protein (BMP)-secreting PDGFRAhi myofibroblast aggregates. BMP signaling inhibits ISC-trophic genes in PDGFRAlo cells near high crypt tiers; that suppression is relieved in stromal cells near and below the crypt base, including trophocytes. Cell distances thus underlie a self-organized and polar ISC niche.
2023-02-21 | GSE211275 | GEO
Project description:Signals from the surrounding niche drive proliferation and suppress differentiation of intestinal stem cells (ISCs) at the bottom of intestinal crypts. Among sub-epithelial support cells, deep sub-cryptal CD81+ PDGFRAlo trophocytes alone sustain ISC functions ex vivo. Here we show that mRNA and chromatin profiles of abundant CD81- PDGFRAlo stromal cells resemble those of trophocytes and that both populations provide crucial canonical Wnt ligands. Mesenchymal expression of key ISC-supportive factors extends along a spatial and molecular continuum from trophocytes into peri-cryptal CD81- CD55hi cells, which mimic trophocyte activity in organoid co-cultures. Graded expression of essential niche factors is not cell-autonomous but dictated by the distance from bone morphogenetic protein (BMP)-secreting PDGFRAhi myofibroblast aggregates. BMP signaling inhibits ISC-trophic genes in PDGFRAlo cells near high crypt tiers and that suppression is relieved in stromal cells near and below the crypt base, including trophocytes. Cell distances thus underlie a self-organized and polar ISC niche.
2023-03-01 | GSE212601 | GEO
Project description:Wnt/b-catenin signaling supports intestinal homeostasis by regulating proliferation in the crypt. Multiple Wnts are expressed in Paneth as well as other intestinal epithelial and stromal cells. Ex vivo, Wnts secreted by Paneth cells can support intestinal stem cells when Wnt signaling is enhanced with supplemental R-Spondin 1 (RSPO1). However, in vivo, the source of Wnts in the stem cell niche is less clear. Genetic ablation of Porcn, an endoplasmic reticulum resident O-acyltransferase that is essential for the secretion and activity of all vertebrate Wnts, confirmed the role of intestinal epithelial Wnts in ex vivo culture. Unexpectedly, mice lacking epithelial Wnt activity (PorcnDel/Villin-Cre mice) had normal intestinal proliferation and differentiation, as well as successful regeneration after radiation injury, indicating epithelial Wnts are dispensable for these processes. Consistent with a key role for stroma in the crypt niche, intestinal stromal cells endogenously expressing Wnts and Rspo3 support the growth of PorcnDel organoids ex vivo without RSPO1 supplementation. Conversely, increasing pharmacologic PORCN inhibition, affecting both stroma and epithelium, reduced Lgr5 intestinal stem cells, inhibited recovery from radiation injury, and at the highest dose fully blocked intestinal proliferation. We conclude that epithelial Wnts are dispensable, and that stromal production of Wnts can fully support normal murine intestinal homeostasis. Microarray was performed on samples enriched for stromal or epithelial cells from small intestine from Porcn(Del)/Villin-Cre and Porcn(WT)/Villin-Cre male C57Bl/6 mice.
2014-04-19 | E-GEOD-56911 | biostudies-arrayexpress
Project description:Wnt/b-catenin signaling supports intestinal homeostasis by regulating proliferation in the crypt. Multiple Wnts are expressed in Paneth as well as other intestinal epithelial and stromal cells. Ex vivo, Wnts secreted by Paneth cells can support intestinal stem cells when Wnt signaling is enhanced with supplemental R-Spondin 1 (RSPO1). However, in vivo, the source of Wnts in the stem cell niche is less clear. Genetic ablation of Porcn, an endoplasmic reticulum resident O-acyltransferase that is essential for the secretion and activity of all vertebrate Wnts, confirmed the role of intestinal epithelial Wnts in ex vivo culture. Unexpectedly, mice lacking epithelial Wnt activity (PorcnDel/Villin-Cre mice) had normal intestinal proliferation and differentiation, as well as successful regeneration after radiation injury, indicating epithelial Wnts are dispensable for these processes. Consistent with a key role for stroma in the crypt niche, intestinal stromal cells endogenously expressing Wnts and Rspo3 support the growth of PorcnDel organoids ex vivo without RSPO1 supplementation. Conversely, increasing pharmacologic PORCN inhibition, affecting both stroma and epithelium, reduced Lgr5 intestinal stem cells, inhibited recovery from radiation injury, and at the highest dose fully blocked intestinal proliferation. We conclude that epithelial Wnts are dispensable, and that stromal production of Wnts can fully support normal murine intestinal homeostasis.
2014-04-19 | GSE56911 | GEO
Project description:Smallbone2013 - Colon Crypt cycle - Version 0
This model is described in the article:
A mathematical model of the colon crypt capturing compositional dynamic interactions between cell types
Kieran Smallbone, Bernard M. Corfe
Int J Exp Pathol. 2014 Feb;95(1):1-7.
Abstract:
Models of the development and early progression of colorectal cancer are based upon understanding the cycle of stem cell turnover, proliferation, differentiation and death. Existing crypt compartmental models feature a linear pathway of cell types, with little regulatory mechanism. Previous work has shown that there are perturbations in the enteroendocrine cell population of macroscopically normal crypts, a compartment not included in existing models. We show that existing models do not adequately recapitulate the dynamics of cell fate pathways in the crypt. We report the progressive development, iterative testing and fitting of a developed compartmental model with additional cell types, and which includes feedback mechanisms and cross-regulatory mechanisms between cell types. The fitting of the model to existing data sets suggests a need to invoke cross-talk between cell types as a feature of colon crypt cycle models.
This model is hosted on BioModels Database
and identified
by: MODEL1306190000
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication
for more information.
2024-09-02 | BIOMD0000000520 | BioModels
Project description:Smallbone2013 - Colon Crypt cycle - Version 1
This model is described in the article:
A mathematical model of the colon crypt capturing compositional dynamic interactions between cell types
Kieran Smallbone, Bernard M. Corfe
Int J Exp Pathol. 2014 Feb;95(1):1-7.
Abstract:
Models of the development and early progression of colorectal cancer are based upon understanding the cycle of stem cell turnover, proliferation, differentiation and death. Existing crypt compartmental models feature a linear pathway of cell types, with little regulatory mechanism. Previous work has shown that there are perturbations in the enteroendocrine cell population of macroscopically normal crypts, a compartment not included in existing models. We show that existing models do not adequately recapitulate the dynamics of cell fate pathways in the crypt. We report the progressive development, iterative testing and fitting of a developed compartmental model with additional cell types, and which includes feedback mechanisms and cross-regulatory mechanisms between cell types. The fitting of the model to existing data sets suggests a need to invoke cross-talk between cell types as a feature of colon crypt cycle models.
This model is hosted on BioModels Database
and identified
by: MODEL1306190001
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication
for more information.
2024-09-02 | BIOMD0000000519 | BioModels
Project description:Smallbone2013 - Colon Crypt cycle - Version 2
This model is described in the article:
A mathematical model of the colon crypt capturing compositional dynamic interactions between cell types
Kieran Smallbone, Bernard M. Corfe
Int J Exp Pathol. 2014 Feb;95(1):1-7.
Abstract:
Models of the development and early progression of colorectal cancer are based upon understanding the cycle of stem cell turnover, proliferation, differentiation and death. Existing crypt compartmental models feature a linear pathway of cell types, with little regulatory mechanism. Previous work has shown that there are perturbations in the enteroendocrine cell population of macroscopically normal crypts, a compartment not included in existing models. We show that existing models do not adequately recapitulate the dynamics of cell fate pathways in the crypt. We report the progressive development, iterative testing and fitting of a developed compartmental model with additional cell types, and which includes feedback mechanisms and cross-regulatory mechanisms between cell types. The fitting of the model to existing data sets suggests a need to invoke cross-talk between cell types as a feature of colon crypt cycle models.
This model is hosted on BioModels Database
and identified
by: MODEL1306190002
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication
for more information.
2024-09-02 | BIOMD0000000518 | BioModels
Project description:Smallbone2013 - Colon Crypt cycle - Version 3
This model is described in the article:
A mathematical model of the colon crypt capturing compositional dynamic interactions between cell types
Kieran Smallbone, Bernard M. Corfe
Int J Exp Pathol. 2014 Feb;95(1):1-7.
Abstract:
Models of the development and early progression of colorectal cancer are based upon understanding the cycle of stem cell turnover, proliferation, differentiation and death. Existing crypt compartmental models feature a linear pathway of cell types, with little regulatory mechanism. Previous work has shown that there are perturbations in the enteroendocrine cell population of macroscopically normal crypts, a compartment not included in existing models. We show that existing models do not adequately recapitulate the dynamics of cell fate pathways in the crypt. We report the progressive development, iterative testing and fitting of a developed compartmental model with additional cell types, and which includes feedback mechanisms and cross-regulatory mechanisms between cell types. The fitting of the model to existing data sets suggests a need to invoke cross-talk between cell types as a feature of colon crypt cycle models.
This model is hosted on BioModels Database
and identified
by: MODEL1306190003
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication
for more information.
2024-09-02 | BIOMD0000000517 | BioModels
Project description:Abdominal and pelvic radiotherapy (RT) reduces the renewal capacity of the epithelium. Rectal biopsies obtained from patients receiving pelvic RT have revealed atrophy of surface epithelium, acute cryptitis, crypt abscesses, crypt distortion and atrophy, and stromal inflammation. Modifications in intestinal microbiota, such as an increase in the number of pathogens, may contribute to intestinal injury. The prebiotic effect of a carbohydrate is assessed by its capacity to stimulate the proliferation of healthy bacteria (Bifidobacterium, Lactobacillus) rather than pathogenic bacteria (Clostridium, E. coli).
The hypothesis of the study is that a mixture of inulin and fructooligosaccharide could modulate Lactobacillus and Bifidobacterium and reduce the intestinal injury in patients affected of gynaecological cancer and treated with abdominal radiotherapy.
| 2121634 | ecrin-mdr-crc
Project description:We demonstrate single-cell RNA sequencing with time course study on DSS-induced colitis mouse model to reveal the overall cellular status during colon inflammation. Based on single cell transcriptome analysis in inflamed colon, we showed that the stromal cell population of colon functions as a hub to coordinate dynamic change with other cell type. We also found the Serpina3n, a serine protease inhibitor is specific up-regulation in the stromal cells during the resolution phase of colon inflammation. Furthermore, we found that systemic administration of Serpina3n promoted the recovery of resolution phase and ameliorated colitis-related symptoms. This study provides a comprehensive understanding of cell-cell interactions during colorectal inflammation at the single-cell level and reveals a potential therapeutic target by hijacking the endogenous inflammation resolution mechanism.
2021-09-03 | GSE148794 | GEO