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| Status |
Public on May 19, 2020 |
| Title |
Functional genomics of human colon organoids (ATAC-Seq) |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
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.
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| Overall design |
IDR OMNI-ATAC-seq profiles of open chromatin were generated from 2 independent replicates of libraries for Caco2 cells and Human intestinal organoids
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| Contributor(s) |
Harris A, Yin S, Kerschner JL |
| Citation(s) |
32390556 |
| |
| Submission date |
Nov 15, 2019 |
| Last update date |
May 19, 2020 |
| Contact name |
Ann Harris |
| E-mail(s) |
axh575@case.edu
|
| Organization name |
Case Western Reserve Uni
|
| Street address |
10900 Euclid Ave
|
| City |
Cleveland |
| State/province |
OH |
| ZIP/Postal code |
44106 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE140458 |
Functional genomics of human colon organoids |
|
| Relations |
| BioProject |
PRJNA589842 |
| SRA |
SRP230188 |
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