Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Generation Of Human Intestinal Organoids From Cronkhite Canada Syndrome Patients Reveals Serotonin As A Link To Intestinal Proliferation

ABSTRACT: Cronkhite Canada Syndrome (CCS) is a rare, non-inherited polyposis syndrome affecting 1 in a million individuals. Despite over 50 years of CCS cases, the etiopathogenesis and optimal treatment for CCS remains unknown due to the rarity of the disease and lack of model systems. To investigate and better understand the etiology of CCS, we generated human intestinal organoids (HIOs) from intestinal stem cells isolated from two CCS patients. We discovered that CCS HIOs have unique growth characteristics and have increased serotonin (5-hydroxytryptamine, 5HT) positive cells. Further investigation revealed that 5HT can induce HIO proliferation, and inhibition of 5HT results in decreased proliferation in the CCS HIOs. Our findings indicate that dysregulation of 5HT may explain polyposis observed in CCS and provide new insight into regulation of the intestinal stem cell. This work illustrates the important contribution organoids can make to understanding disease etiology and identifying novel therapies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE207838 | GEO | 2023/08/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

scRNA-seq of hPSC-derived human intestinal organoids with endogenous vascular endothelial cells

Project description:The development of human pluripotent stem cell (hPSC)- derived small intestinal organoids (HIOs) has led to an improved understanding of human intestinal development and physiology. HIOs generated using directed differentiation lack some cellular populations found in the native organ, including vasculature. We performed single cell RNA sequencing (scRNA-seq) on approximately 13,000 cells at various timepoints (0, 3, 7, and 14 days) across HIO in vitro development and observed a transient population of endothelial-like cells (ECs) present within HIOs early during differentiation. Our data demonstrate that EC-like cells fail to be robustly maintained in long term culture. Here, we have developed a new directed differentiation approach to enhance co-differentiation and maintenance of ECs within HIOs, leading to the development of vascularized HIOs (vHIOs). scRNAseq was used to compare vHIOs to control HIOs after 59d months in culture.

2020-12-20 | E-MTAB-9228 | biostudies-arrayexpress

RNA-seq of transplanted pluripotent stem cells-derived human intestinal organoids upon mechanical lengthening and human jejunum tissues

Project description:Human Intestinal Organoids (HIOs) generated from embryonic and/or induced pluripotent stem cell lines offer an avenue to study both developmental and human specific disease states. Recently, progress has been made in scaling and maturing these inherently immature tissues through transplanting them in vivo. However, these resultant grafts best approximate fetal intestinal tissue thus limiting their utility. To induce growth and maturation of HIOs we used a nitinol spring device to mechanically induce enterogenesis of HIO in vivo. HIOs are cultured prior to implantation within the mesentery of immunodeficient mice. They are allowed to grow, vascularize, and mature before a second procedure is performed wherein a compressed nitinol spring is implanted within the lumen of the transplanted HIO (tHIO). Next Generation RNA sequencing was performed across transplanted samples as well as on human surgical samples to highlight the transcriptional similarities and differences between groups. Transcriptionally, the tHIO+S samples were more similar to human tissues than the tHIO. With these initial experiments, we concluded that the application of an intraluminal uniaxial force is a practical method to induce maturation of tHIOs in vivo without concomitant architectural disruptions. While our current system does lack certain complexities, we have demonstrated enterogenesis by means of mechanical manipulation.

2018-03-30 | E-MTAB-6017 | biostudies-arrayexpress

Particulate matter 10 exposure affects intestinal functionality in both inflamed 2D intestinal epithelial cell and 3D intestinal organoid models

Project description:A growing body of evidence suggests that particulate matter (PM10) enters the gastrointestinal (GI) tract directly, causing the GI epithelial cells to function less efficiently, leading to inflammation and an imbalance in the gut microbiome. PM10 may, however, act as an exacerbation factor in patients with inflamed intestinal epithelium, which is associated with inflammatory bowel disease. In this study, we established chronically inflamed intestinal epithelium models utilizing two-dimensional (2D) human intestinal epithelial cells (hIECs) and 3D human intestinal organoids (hIOs), which mimic in vivo cellular diversity and function, in order to examine the deleterious effects of PM10 in human intestine-like in vitro models. Inflamed 2D hIECs and 3D hIOs exhibited pathological features, such as inflammation, decreased intestinal markers, and defective epithelial barrier function. In addition, we found that PM10 exposure induced a more severe disturbance of peptide uptake in inflamed 2D hIECs and 3D hIOs than in control cells. This was due to the fact that it interferes with calcium signaling, protein digestion, and absorption pathways. The findings demonstrate that PM10-induced epithelial alterations contribute to the exacerbation of inflammatory disorders caused by the intestine. According to our findings, 2D hIEC and 3D hIO models could be powerful in vitro platforms for the evaluation of the causal relationship between PM exposure and abnormal human intestinal functions.

2023-07-19 | GSE227514 | GEO

Functional genomics of human colon organoids (ATAC-Seq)

Project description:Organoids are a valuable 3D model to study the differentiated functions of the human intestinal epithelium. They are a particularly powerful tool to measure epithelial transport processs in health and disease. Though biological assays such as organoid swelling and intraluminal pH measurements are well established, their underlying functional genomics are not well characterized. Here we combine genome-wide analysis of open chromatin by ATAC-seq with transcriptome mapping by RNA-seq to define the genomic signature of human intestinal organoids (HIOs). These data provide an important tool for investigating key physiological and biochemical processes in the intestinal epithelium. We next compared the transcriptome and open chromatin profiles of HIOs with equivalent datasets from the Caco2 colorectal carcinoma line, which is an important 2D model of the intestinal epithelium. Our results define common features of the intestinal epithelium in HIO and Caco2 and further illustrate the cancer-associated program of the cell line. Generation of Caco2 organoids enabled interrogation of the molecular divergence of the 2D and 3D cultures. Over-represented motif analysis of open chromatin peaks identified Caudal Type Homeobox 2 (CDX2) as a key activating transcription factor in HIO, but not in monolayer cultures of Caco2. However, the CDX2 motif becomes overrepresented in open chromatin from Caco2 organoids, reinforcing the importance of this factor in intestinal epithelial differentiation and function. Intersection of the HIO and Caco2 transcriptomes further showed functional overlap in pathways of ion transport and tight junction integrity among others. These data make an important contribution to understanding human intestinal organoid biology.

2020-05-19 | GSE140456 | GEO

Functional genomics of human colon organoids (RNA-Seq)

2020-05-19 | GSE140455 | GEO

In vitro maturation of human pluripotent stem cell-derived intestinal organoids

Project description:Human intestinal organoids (hIOs) derived from human pluripotent stem cells (hPSCs) have immense potential as a source of intestines. However, due to problems obtaining mature adult-like cells from hPSCs, effective strategies for the maturation of hIOs with improved functionalities must be developed. We established conditions that enable the in vitro maturation of hIOs derived from hPSCs, recapitulating the essential features of intestinal tissue. The maturity of the hPSC-derived hIOs was enhanced by the in vitro maturation in our co-culture system, evidenced by transcriptional changes observed in our microarray data. Global transcription of in vitro-matured hIOs is highly similar to that of adult human small intestine (hSI). Compared to control hIOs, in vitro-matured hIOs exhibited significant increases in the expression of intestinal maturation markers, major transporters, and key enzymes for drug absorption and first-pass metabolism.

2018-08-27 | GSE116738 | GEO

scRNA-seq of pluripotent stem cell derived human intestinal organoids

Project description:Here, we used single cell RNA-sequencing (scRNA-seq) to profile pluripotent stem cell derived human intestinal organoids (HIOs) grown in matrigel or a non-adhesive alginate hydrogel after 28 days of in vitro growth. Additionally, we used scRNA-seq to profile HIOs derived in the presence of Neuregulin 1 (NRG1) and/or EGF after 40 days of in vitro growth.

2021-05-21 | E-MTAB-10268 | biostudies-arrayexpress

Epithelial maturation of human intestinal organoids from pluripotency entirely in vitro

Project description:In vitro human pluripotent stem cell derived intestinal organoids (HIOs) are immature and lack for diverse differentiated secretory cell types. We would like to test the hypothesis whether addition of a mesenchyme secreting ligand which is depleted in canonical organoid culture media could increase the maturity and secretory cell type diversity in HIOs in vitro. To do this, we adapted the directed differentiation protocol of HIOs by growing HIOs in media with EGF, NOGGIN, R-spondin-1 (ENR) for 30 days, isolated epithelial cells with dispase, recovered them with adult intestinal enteroid media with Wnt-3A (WENR). Then we introduced the mesenchyme secreting ligand NRG1 to the established enteroid culture (WENR+NRG1) and compared them to the enteroids grown in control condition (WENR).

2022-12-31 | E-MTAB-10876 | biostudies-arrayexpress

In vitro maturation of intestinal organoids differentiated from wild type and STAT3 knock out human embryonic stem cells

Project description:Human intestinal organoids (hIOs) resemble the human intestine physiologically and structurally. We recently present an in vitro maturation technique for generating mature and functional hIOs from human pluripotent stem cells (hPSCs). Here, we investigated the mechanisms of STAT3 for inducing in vitro maturation of hIOs. Using CRISPR/Cas9-mediated gene editing, STAT3 knockout (KO) human embryonic stem cell (hESC) lines were generated and characterized. By genome-wide microarray analyses, STAT3 KO hIOs showed markedly different profiles from the in vitro matured hIOs and human small intestine and the majority of genes, which are associated with intestinal development and functions, were downregulated by STAT3 KO. This study reveals important signaling pathways for the maturation of hIOs derived from hPSCs.

2019-09-30 | GSE132561 | GEO

scRNA-seq of pluripotent stem cell derived human intestinal organoids grown in suspension culture

Project description:Here, we used single-cell RNA-sequencing (scRNA-seq) to profile pluripotent stem cell derived human intestinal organoids (HIOs) grown in suspension culture after 28 days of in vitro growth. Grown in minigut media supplemented with EGF.

2022-02-04 | E-MTAB-11347 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data