Ethanol exposure drives colon location-specific cell composition changes in a normal colon crypt 3D organoid model
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA630954 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11727800_1.fastq.gz | Fastqsanger.gz | |||
| SRR11727800_2.fastq.gz | Fastqsanger.gz | |||
| SRR11727801_1.fastq.gz | Fastqsanger.gz | |||
| SRR11727801_2.fastq.gz | Fastqsanger.gz | |||
| SRR11727802_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Here, we used bulk RNA-seq data derived from healthy colon organoids (un)exposed to ethanol. Through the use of external single cell RNA-seq data, we estimate changes in cell composition that are more pronounced in distal colon organoids following ethanol treatment. We extend this analysis by inferring cell-type-specific effects of ethanol treatment on colon organoids.
2020-12-14 | GSE150027 | GEO
Project description:Alcohol is a consistently identified risk factor for colon cancer. However, the molecular mechanism underlying its effect on normal colon crypt cells remains poorly understood. We employed RNA-sequencing to asses transcriptomic response to ethanol exposure (0.2% vol:vol) in 3D organoid lines derived from healthy colon (n = 34). Paired regression analysis identified 2,162 differentially expressed genes in response to ethanol. When stratified by colon location, a far greater number of differentially expressed genes were identified in organoids derived from the left versus right colon, many of which corresponded to cell-type specific markers. To test the hypothesis that the effects of ethanol treatment on colon organoid populations were in part due to differential cell composition, we incorporated external single cell RNA-sequencing data from normal colon biopsies to estimate cellular proportions following single cell deconvolution. We inferred cell-type-specific changes, and observed an increase in transit amplifying cells following ethanol exposure that was greater in organoids from the left than right colon, with a concomitant decrease in more differentiated cells. If this occurs in the colon following alcohol consumption, this would lead to an increased zone of cells in the lower crypt where conditions are optimal for cell division and the potential to develop mutations.
| S-EPMC7801615 | biostudies-literature
Project description:Lgr5+ stem cells reside at crypt bottoms of the small and large intestine. Small intestinal Paneth cells supply Wnt3, EGF and Notch signals to neighboring Lgr5+ stem cells. While the colon lacks Paneth cells, Deep Crypt Secretory (DCS) cells are intermingled with Lgr5+ stem cells at crypt bottoms. Here, we report Reg4 as a marker of DCS cells. To investigate a niche function, we eliminated DCS cells using the diphtheria-toxin receptor gene knocked into the murine Reg4 locus. Ablation of DCS cells results in loss of stem cells from colonic crypts and disrupts gut homeostasis and colon mini-gut formation. In agreement, sorted Reg4+ DCS cells promote organoid formation of single Lgr5+ colon stem cells. Stem cells are forced to generate DCS cells in vitro by combined Notch inhibition and Wnt activation. We conclude that Reg4+ DCS cells serve as Paneth cell equivalents in the colon crypt niche.
2016-10-05 | GSE63256 | GEO
Project description:Transcriptomic profiles of 6 commercially-available human patient-derived gastrointestinal organoid lines were obtained and compared to transcriptomic profile of a commercially available human iPSC-induced colon organoid line. Transcriptomic profile of iPSC-derived human colon organoid line was compared after culture in either Corning growth-factor-reduced Matrigel (Corning 356231) or MilliporeSigma growth-factor-reduced ECMGel (E6909)
2022-03-31 | E-MTAB-11557 | biostudies-arrayexpress
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 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 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 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:It is not known why cancers arising in anatomically distinct locations but within the same tissue type can exhibit stark differences in molecular, pathological and clinical features. Cancers arising in proximal and distal sites of the colon are emblematic of these above differences as the proximal and distal colon cancers harbor differences in key molecular features, with BRAFV600E oncogene predominantly occurring in proximal colon cancers in the context of the increased promoter DNA methylation phenotype (CIMP-high), while distal colon cancers lack these molecular features. We determined the molecular basis of tissue-location specificity of driver mutations using normal mouse derived organoid models for colon cancer initiation. We show that the homeobox transcription factor, Cdx2, which is downregulated by DNA methylation in proximal colon cancers, plays distinct roles in regulating stem cell and differentiation in proximal compared to distal colon stem cells. Loss of Cdx2 altered the differentiation and stem cell programs and result in transformation by BRAFV600E specifically in the proximal but not distal colon stem cells. Analyses of RNA expression and Cdx2-binding to target genomic regions revealed that Cdx2 was a key effector of the transcriptional response to differentiation cues in proximal colon cells. This proximal colon-specific transcriptional program concurrently is tumor suppressive, and its loss sufficiently creates permissive state for oncogenic-BRAF mutations. The transcriptional program associated with Cdx2 loss in mouse proximal organoids matches that of human proximal colon cancers with downregulated CDX2 expression due to epigenetic silencing. Our analyses reveal that developmental and lineage-restricted transcription factors maintain tissue-location specific transcriptional programs which create critical dependencies for tumor initiation.
2023-12-12 | GSE218479 | GEO
Project description:It is not known why cancers arising in anatomically distinct locations but within the same tissue type can exhibit stark differences in molecular, pathological and clinical features. Cancers arising in proximal and distal sites of the colon are emblematic of these above differences as the proximal and distal colon cancers harbor differences in key molecular features, with BRAFV600E oncogene predominantly occurring in proximal colon cancers in the context of the increased promoter DNA methylation phenotype (CIMP-high), while distal colon cancers lack these molecular features. We determined the molecular basis of tissue-location specificity of driver mutations using normal mouse derived organoid models for colon cancer initiation. We show that the homeobox transcription factor, Cdx2, which is downregulated by DNA methylation in proximal colon cancers, plays distinct roles in regulating stem cell and differentiation in proximal compared to distal colon stem cells. Loss of Cdx2 altered the differentiation and stem cell programs and result in transformation by BRAFV600E specifically in the proximal but not distal colon stem cells. Analyses of RNA expression and Cdx2-binding to target genomic regions revealed that Cdx2 was a key effector of the transcriptional response to differentiation cues in proximal colon cells. This proximal colon-specific transcriptional program concurrently is tumor suppressive, and its loss sufficiently creates permissive state for oncogenic-BRAF mutations. The transcriptional program associated with Cdx2 loss in mouse proximal organoids matches that of human proximal colon cancers with downregulated CDX2 expression due to epigenetic silencing. Our analyses reveal that developmental and lineage-restricted transcription factors maintain tissue-location specific transcriptional programs which create critical dependencies for tumor initiation.
2023-12-12 | GSE218480 | GEO