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| Status |
Public on Jan 01, 2025 |
| Title |
The conserved disulfide isomerase PDIA3/ERp60 regulates intestinal epithelial homeostasis in response to shifts in ether phospholipid metabolism. |
| Organism |
Drosophila melanogaster |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Intestinal epithelium regeneration and homeostasis must be tightly regulated. Alteration of epithelial homeostasis is a major contributing factor to diseases such as colorectal cancer and inflammatory bowel diseases. Many pathways involved in epithelial regeneration have been identified, but more regulators remain undiscovered. Metabolism has emerged as an overlooked regulator of intestinal epithelium homeostasis. Using the model organism Drosophila melanogaster, we found that ether lipid metabolism is required to maintain intestinal epithelial homeostasis. Its dysregulation in intestinal progenitors causes the activation of the unfolded protein response of the endoplasmic reticulum (UPR) that activates Xbp1 and upregulates the disulfide isomerase PDIA3/ERp60. Activation of the Xbp1-ERp60 signaling causes Jak/Stat-mediated increase in progenitor cells, compromising epithelial barrier function and survival in males but not females. This study identified ether lipids-PDIA3/ERp60 as a key regulator of intestinal progenitor homeostasis in health that, if altered, causes pathological conditions in the intestinal epithelium.
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| Overall design |
FACS-isolated Drosophila wildtype and Pex5-depleted intestinal progenitor cells.
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| Contributor(s) |
Makdissi S, Loudhaief R, George S, Weller T, Salim M, Malik A, Mu Y, Parsons BD, Di Cara F |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| BioProject |
PRJNA1189839 |
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| Submission date |
Dec 10, 2024 |
| Last update date |
Jan 01, 2025 |
| Contact name |
Francesca Di Cara |
| Organization name |
Dalhousie University
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| Street address |
5850/5980 University Avenue
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| City |
Halifax |
| State/province |
Nova Scotia |
| ZIP/Postal code |
B3K 6R8 |
| Country |
Canada |
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| Platforms (1) |
| GPL25244 |
Illumina NovaSeq 6000 (Drosophila melanogaster) |
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| Samples (6)
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| GSM8674264 |
Intestinal stem cell, experimental, rep1 |
| GSM8674265 |
Intestinal stem cell, experimental, rep2 |
| GSM8674266 |
Intestinal stem cell, experimental, rep3 |
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| Supplementary file |
Size |
Download |
File type/resource |
| GSE283923_Counts_QIAseqUltraplexRNA.xlsx |
2.2 Mb |
(ftp)(http) |
XLSX |
| GSE283923_FoldChanges_Dseq.txt.gz |
237.5 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
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