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Status |
Public on Jul 19, 2018 |
Title |
In vivo replacement of damaged bladder urothelium by Wolffian duct epithelial cells |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
The bladder’s remarkable regenerative capacity in response to injury had been thought to reside exclusively in its basal and intermediate cells. While examining consequences of DNA methyltransferase 1 (Dnmt1) inactivation in mouse embryonic bladder epithelium, we made the surprising discovery that Wolffian duct epithelial cells also support bladder regeneration. Conditional inactivation of Dnmt1 in mouse urethral and bladder epithelium triggered widespread apoptosis, depleted basal and intermediate bladder cells and disrupted Uroplakin protein expression. These events coincided with recruitment of Wolffian duct epithelial cells into Dnmt1 mutant urethra and bladder where they were reprogrammed to express bladder markers including FOXA1, Keratin 5, P63 and Uroplakin. This is the first evidence that Wolffian duct epithelial cells can be summoned in vivo to replace damaged bladder epithelium and function as a cell reservoir for bladder regeneration.
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Overall design |
Bladder urothelium were separated from stroma tissues and profiled by RNA-seq. Total 14 samples, from E15.5 embryos with three different genotypes ( including conditional Dnmt1 KO in the bladder urothelium, detailed in sample list characteristics: genotypes)
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Contributor(s) |
Joseph DB, Vezina CM, Chu L |
Citation(s) |
30061411 |
NIH grant(s) |
Grant ID |
Grant title |
Affiliation |
Name |
R01 DK099328 |
Role of DNA methylation in prostate glandular development and urinary function |
UNIVERSITY OF WISCONSIN MADISON |
CHAD M. VEZINA |
U54 DK104309 |
The Genetic Origins and Complications of Urinary Tract Abnormalities |
Trustees of Columbia University in the City of New York |
CATHY Lee MENDELSOHN |
R01 DK095044 |
Retinoic acid signaling controls urothelial development and regeneration. |
Trustees of Columbia University in the City of New York |
CATHY Lee MENDELSOHN |
U01 DK110807 |
Molecular and fate maps of prostatic stroma |
UNIVERSITY OF WISCONSIN MADISON |
CHAD M. VEZINA |
U54 DK104310 |
Role of Beta-Catenin in Urinary Dysfunction |
UNIVERSITY OF WISCONSIN MADISON |
CHAD M. VEZINA |
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Submission date |
Jun 07, 2018 |
Last update date |
Feb 11, 2019 |
Contact name |
Chad Michael Vezina |
Organization name |
University of Wisconsin-Madison
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Department |
Comparative Biosciences
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Street address |
1656 Linden Drive
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City |
Madison |
State/province |
WI |
ZIP/Postal code |
53706 |
Country |
USA |
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Platforms (1) |
GPL21493 |
Illumina HiSeq 3000 (Mus musculus) |
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Samples (14)
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Relations |
BioProject |
PRJNA475133 |
SRA |
SRP150004 |