|
| Status |
Public on Nov 15, 2019 |
| Title |
DNA methylation regulates nephron progenitor cell renewal and differentiation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Nephron number is a major determinant of long-term renal function. We hypothesized a link between epigenetic regulation and nephron formation. In support of this hypothesis, expression analysis evidenced high levels of DNA methyltransferases Dnmt1 and Dnmt3a in the nephrogenic zone of the developing mouse kidney. Using targeted loss-of-function manipulations in mice, we show that deletion of Dnmt1 in nephron progenitor cells results in a marked hypoplasia and reduction of nephron number at birth. In contrast, deletion of Dnmt3a/3b in nephron progenitor cells or deletion of Dnmt1/3a/3b in differentiated renal cells did not lead to any overt kidney phenotype. Whole mount optical projection tomography and 3D-reconstructions uncovered a significant reduction of stem cell niches and progenitor cells in Dnmt1-deficient mice. Ultimately, RNA sequencing analysis revealed that Dnmt1 controls DNA transcription regulating progenitor renewal, identity and differentiation. In summary, this study establishes DNA methylation as key regulatory event of prenatal renal programming.
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| |
|
| Overall design |
RNA-seq of FACS-sorted cap mesenchyme of E18.5 Six2.Cre;Dnmt1 conditional heterozygous and homozygous knockout mice
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| |
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| Contributor(s) |
Wanner N, Boerries M, Busch H, Bechtel-Walz W, Huber TB |
| Citation(s) |
30518531, 34944697 |
| |
| Submission date |
Jan 26, 2017 |
| Last update date |
Jan 10, 2022 |
| Contact name |
Nicola Wanner |
| E-mail(s) |
nicola.wanner@uniklinik-freiburg.de
|
| Organization name |
University Medical Center Freiburg
|
| Department |
Renal Division
|
| Street address |
Breisacherstraße 66
|
| City |
Freiburg |
| ZIP/Postal code |
79106 |
| Country |
Germany |
| |
|
| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (6)
|
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| Relations |
| BioProject |
PRJNA368816 |
| SRA |
SRP097866 |
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