|
| Status |
Public on Aug 10, 2018 |
| Title |
Inactivation of transcription factor HNF-1β with CRISPR/Cas9 induces epithelial-mesenchymal transition |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Hepatocyte nuclear factor-1β (HNF-1β) is a tissue-specific transcription factor that is essential for the development of the kidney. Mutations of HNF-1β produce autosomal dominant tubulointerstitial kidney disease (ADTKD) characterized by tubular cysts, renal fibrosis, and progressive decline in kidney function. To understand the functions of HNF-1β, we generated HNF-1β-deficient mIMCD3 renal epithelial cells. Gene editing with CRISPR/Cas9 was used to delete exon 1 of HNF-1β by non-homologous end joining (NHEJ). We performed RNA-seq on three independent HNF-1β-deficient mIMCD3 cell lines and three paired control cell lines. Our RNA-seq of HNF-1β-deficient cells showed upregulation of 1,135 genes and repression of 759 genes compared to control cells. Pathway analysis revealed that fibrosis and epithelial-mesenchymal transition (EMT) pathways were highly activated in HNF-1β-deficient cells. We conclude that loss of HNF-1β in renal epithelial cells leads to the activation of a transcriptional network that induces EMT and aberrant TGFβ signaling. Targeting this network may inhibit fibrosis in ADTKD and other chronic kidney diseases.
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| |
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| Overall design |
RNA-seq of three independent HNF-1β-deficient mIMCD3 cell lines and three paired control cell lines.
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| |
|
| Contributor(s) |
Igarashi P, Chan SC |
| Citation(s) |
30097458 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R37 DK042921 |
Regulation of Kidney-Specific Gene Expression |
UNIVERSITY OF MINNESOTA |
Peter Igarashi |
|
| |
| Submission date |
Apr 13, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Siu Chiu Chan |
| E-mail(s) |
chanx159@umn.edu
|
| Phone |
612-625-1881
|
| Organization name |
University of Minnesota
|
| Department |
Medicine
|
| Lab |
Dr. Peter Igarashi
|
| Street address |
MCB-5148 420 Washington Ave SE
|
| City |
Minneapolis |
| State/province |
MN |
| ZIP/Postal code |
55455 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (6)
|
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| Relations |
| BioProject |
PRJNA382838 |
| SRA |
SRP103916 |
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