Journal article
DNA Methyltransferase 1 Controls Nephron Progenitor Cell Renewal and Differentiation
Nicola Wanner, Julia Vornweg, Alexander Combes, Sean Wilson, Julia Plappert, Gesa Rafflenbeul, Victor G Puelles, Raza-Ur Rahman, Timur Liwinski, Saskia Lindner, Florian Grahammer, Oliver Kretz, Mary E Wlodek, Tania Romano, Karen M Moritz, Melanie Boerries, Hauke Busch, Stefan Bonn, Melissa H Little, Wibke Bechtel-Walz Show all
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | AMER SOC NEPHROLOGY | Published : 2019
Abstract
BACKGROUND: Nephron number is a major determinant of long-term renal function and cardiovascular risk. Observational studies suggest that maternal nutritional and metabolic factors during gestation contribute to the high variability of nephron endowment. However, the underlying molecular mechanisms have been unclear. METHODS: We used mouse models, including DNA methyltransferase (Dnmt1, Dnmt3a, and Dnmt3b) knockout mice, optical projection tomography, three-dimensional reconstructions of the nephrogenic niche, and transcriptome and DNA methylation analysis to characterize the role of DNA methylation for kidney development. RESULTS: We demonstrate that DNA hypomethylation is a key feature of ..
View full abstractGrants
Awarded by Collaborative Research Centre 992 Medical Epigenetics (Deutsche Forschungsgesellschaft [DFG])
Awarded by German Federal Ministry of Education and Research (Bundesministerium fur Bildung und Forschung [BMBF])
Awarded by Marie Curie European Union grant
Awarded by German Research Foundation (DFG)
Awarded by European Research Council
Awarded by H2020-IMI2 consortium BEAt-DKD (Biomarker Enterprise to Attack Diabetic Kidney Disease)
Awarded by STOP-FSGS (Speed Translation-Oriented Progress to Treat Focal Segmental Glomerulosclerosis)
Awarded by National Health and Medical Research Council
Awarded by German Federal Ministry of Education and Research (BMBF)
Funding Acknowledgements
The Galaxy server that was used for some calculations is in part funded by Collaborative Research Centre 992 Medical Epigenetics (Deutsche Forschungsgesellschaft [DFG] grant SFB 992/1 2012) and the German Federal Ministry of Education and Research (Bundesministerium fur Bildung und Forschung [BMBF] grants 031 A538A/A538C RBC, 031L0101B/031L0101C de. NBI-epi, 031L0106 de.STAIR [de.NBI]). This work is supported by a Marie Curie European Union grant (CIG 293568) (to W.B.-W.), the Margarete von Wrangell Habilitationsprogramm (Ministerium fur Wissenschaft Baden-Wurttemberg) (to W.B.-W.), and the Mathilde-Wagner-Habilitationspreis (to W.B.-W.). Furthermore, this study was supported by the German Research Foundation (DFG): CRC 1140 (to T.B.H.), CRC 1192 (to T.B.H.), CRC 992 (to T.B.H.), EXE306 (to H.B.), and CRC 850 (to M.B.); by the Heisenberg program (to T.B.H.); by the European Research Council grant 616891 (to T.B.H.); by the H2020-IMI2 consortium BEAt-DKD (Biomarker Enterprise to Attack Diabetic Kidney Disease) (115974, to T.B.H.); by STOP-FSGS (Speed Translation-Oriented Progress to Treat Focal Segmental Glomerulosclerosis) 01GM1518C (to T.B.H.); by the Else-Kroner Fresenius Stiftung (iPRIME [innovative Promotionsforderung im Bereich translationale Entzundungsforschung] and NAKSYS [Nierenfunktionsstorungen als Komplikation von Systemerkrankungen]); by the Excellence Initiative of the German Federal and State Governments (EXC294, BIOSS II to T.B.H.); and by the Freiburg Institute for Advanced Studies (to T.B.H.). M.H.L. is a Senior Principal Research Fellow and V.G.P. is an Early Career Research Fellow of the National Health and Medical Research Council of Australia. A.C. is a Discovery Early Career Researcher Award Fellow of the Australian Research Council. M.H.L., A.C., and S.W. are funded by the National Health and Medical Research Council (ID1063989). V.G.P. is also funded by the Alexander von Humboldt Foundation and the German Society of Nephrology (DGfN). Murdoch Children's Research Institute is supported by the Victorian Government's Operational Infrastructure Support Program. M.B. is funded by the German Federal Ministry of Education and Research (BMBF) within the framework of the e: Med research and funding concept (FKZ (Forschungskennzeichen) 01ZX1409B).