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@ARTICLE{Wanner:310355,
author = {N. Wanner and J. Keller and N. Liaukouskaya and G. Andrieux
and S. D. Laufer and M. Rogg and T. Bork and W. Liang and F.
Braun and F. Haas and M. N. Wong and V. G. Puelles and S. E.
Gies and C. Meyer and M. Boerries$^*$ and M. Helmstädter
and O. Kretz and I. Hild and E. Metzger$^*$ and R. Schüle
and W. Bechtel-Walz and T. B. Huber},
title = {{L}ysine-specific histone demethylase 1a regulates nephron
development and long-term transcriptional programming.},
journal = {JCI insight},
volume = {11},
number = {5},
issn = {2379-3708},
address = {Ann Arbor, Michigan},
publisher = {JCI Insight},
reportid = {DKFZ-2026-00555},
pages = {e190283},
year = {2026},
abstract = {Low nephron endowment constitutes a risk factor for
hypertension and renal disease. Epigenetic regulation is
crucial for nephron progenitor cell differentiation,
affecting nephron number and renal function. The role of
many epigenetic modulators, such as Lysine-specific histone
demethylase 1a (LSD1 or KDM1A), remains unclear. We used
Kdm1a-KO mice to demonstrate that Kdm1a depletion in nephron
progenitor cells results in reduced kidney size in neonates
and led to glomerulosclerosis, proteinuria, and renal cysts
in adults. Notably, Kdm1a deletion in podocytes or tubular
cells did not replicate these effects. CRISPR/Cas9-mediated
KDM1A deletion in human kidney organoids caused cyst
formation and altered gene expression, with snRNA-seq
revealing downregulation of podocyte genes and upregulation
of metabolic genes. The presence of noncoding RNAs indicated
roles in cell proliferation. Our study reveals the critical
role of Kdm1a function in nephron development and highlights
its affect on transcriptional programming for long-term
renal function and susceptibility to cyst formation.},
keywords = {Animals / Nephrons: growth $\&$ development / Nephrons:
metabolism / Nephrons: pathology / Mice / Mice, Knockout /
Histone Demethylases: genetics / Histone Demethylases:
metabolism / Humans / Podocytes: metabolism / Cell
Differentiation: genetics / Cell Proliferation: genetics /
Gene Expression Regulation, Developmental / Male /
Epigenesis, Genetic / Organoids / Chronic kidney disease
(Other) / Development (Other) / Epigenetics (Other) /
Nephrology (Other) / KDM1a protein, mouse (NLM Chemicals) /
Histone Demethylases (NLM Chemicals) / KDM1A protein, human
(NLM Chemicals)},
cin = {FR01},
ddc = {610},
cid = {I:(DE-He78)FR01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41797715},
doi = {10.1172/jci.insight.190283},
url = {https://inrepo02.dkfz.de/record/310355},
}