 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jul 13, 2023 |
| Title |
An organoid-based CRISPR/Cas9 screen for regulators of intestinal epithelial maturation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Other
|
| Summary |
Generation of functionally mature organs requires exquisite control of transcriptional programs governing cell state transitions during development. Despite advances in understanding the behavior of adult intestinal stem cells and their progeny, the transcriptional regulators that control the emergence of the mature intestinal phenotype remain largely unknown. Using mouse fetal and adult small intestinal organoids, we uncover transcriptional differences between the fetal and adult state and identify rare adult-like cells present in fetal organoids. This suggests that fetal organoids possess an inherent potential to mature, which is locked by a regulatory program. By implementing a CRISPR/Cas9 screen targeting transcriptional regulators expressed in fetal organoids, we establish Smarca4 and Smarcc1 as important factors safeguarding the immature progenitor state. Our approach demonstrates the utility of organoid models in the identification of factors regulating cell fate and state transitions during tissue maturation and reveal that Smarca4 and Smarcc1 prevent precocious differentiation during intestinal development.
|
| |
|
| Overall design |
CRISPR screen of transcriptional regulators in mouse intestinal organoids analysed by sgRNA-sequencing and subsequent scRNA-seq, RNA-seq, and ATAC-seq profiling of mutant organoid lines.
|
| |
|
| Contributor(s) |
Hansen SL, Larsen HL, Pikkupeura LM, Maciag G, Guiu J, Müller I, Mueller C, Clement D, Vilstrup Johansen J, Helin K, Lerdrup M, Jensen KB |
| Citation(s) |
37436979 |
| |
| Submission date |
Dec 19, 2022 |
| Last update date |
Sep 11, 2023 |
| Contact name |
Laura Maarit Pikkupeura |
| Organization name |
University of Copenhagen
|
| Department |
BRIC
|
| Lab |
Jensen lab
|
| Street address |
Ole Maaloes vej 5
|
| City |
Copenhagen N |
| ZIP/Postal code |
2200 |
| Country |
Denmark |
| |
|
| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (35)
|
|
| Relations |
| BioProject |
PRJNA913818 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE221278_Enh_ATAC_counts.txt.gz |
1023.9 Kb |
(ftp)(http) |
TXT |
| GSE221278_aOrg.csv.gz |
27.8 Mb |
(ftp)(http) |
CSV |
| GSE221278_all_CRISPR_samples.count.txt.gz |
96.9 Kb |
(ftp)(http) |
TXT |
| GSE221278_counts.txt.gz |
2.3 Mb |
(ftp)(http) |
TXT |
| GSE221278_ctrl.csv.gz |
20.1 Mb |
(ftp)(http) |
CSV |
| GSE221278_fens.csv.gz |
32.4 Mb |
(ftp)(http) |
CSV |
| GSE221278_smarca4.csv.gz |
35.5 Mb |
(ftp)(http) |
CSV |
| GSE221278_smarcc1.csv.gz |
22.1 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...