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| Status |
Public on Jul 01, 2019 |
| Title |
ARID1A and PI3-Kinase pathway mutations in the endometrium drive epithelial transdifferentiation and collective invasion [12Z_RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
ARID1A and PI3-Kinase (PI3K) pathway alterations are common in neoplasms originating from the uterine endometrium. Here we show that monoallelic loss of ARID1A in the mouse endometrial epithelium is sufficient for vaginal bleeding when combined with PI3K activation. Sorted mutant epithelial cells display gene expression and promoter chromatin signatures associated with epithelial-to-mesenchymal transition (EMT). We further show that ARID1A is bound to promoters with open chromatin, but ARID1A loss leads to increased promoter chromatin accessibility and the expression of EMT genes. PI3K activation partially rescues the mesenchymal phenotypes driven by ARID1A loss through antagonism of ARID1A target gene expression, resulting in partial EMT and invasion. We propose that ARID1A normally maintains endometrial epithelial cell identity by repressing mesenchymal cell fates, and that coexistent ARID1A and PI3K mutations promote epithelial transdifferentiation and collective invasion. Broadly, our findings support a role for collective epithelial invasion in the spread of abnormal endometrial tissue.
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| Overall design |
12Z endometriotic epithelial cells transfected with either siARID1A or non-targeting siRNA control were assayed 48 hours post-transfection via RNA-seq.
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| Contributor(s) |
Wilson MR, Reske JJ, Chandler RL |
| Citation(s) |
31391455, 32321567, 35326450 |
| |
| Submission date |
Apr 14, 2019 |
| Last update date |
Mar 31, 2022 |
| Contact name |
Ronald L. Chandler |
| E-mail(s) |
rlc@msu.edu
|
| Organization name |
Michigan State University
|
| Department |
Obstetrics, Gynecology and Reproductive Biology
|
| Street address |
3100-4 400 Monroe NW
|
| City |
Grand Rapids |
| State/province |
MI |
| ZIP/Postal code |
49503 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE121198 |
ARID1A and PI3-Kinase pathway mutations in the endometrium drive epithelial transdifferentiation and collective invasion |
|
| Relations |
| BioProject |
PRJNA532771 |
| SRA |
SRP192521 |
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