TY  - JOUR
AU  - Wanner, Nicola
AU  - Keller, Julia
AU  - Liaukouskaya, Nastassia
AU  - Andrieux, Geoffroy
AU  - Laufer, Sandra D
AU  - Rogg, Manuel
AU  - Bork, Tillmann
AU  - Liang, Wei
AU  - Braun, Fabian
AU  - Haas, Fabian
AU  - Wong, Milagros N
AU  - Puelles, Victor G
AU  - Gies, Sydney E
AU  - Meyer, Charlotte
AU  - Boerries, Melanie
AU  - Helmstädter, Martin
AU  - Kretz, Oliver
AU  - Hild, Iris
AU  - Metzger, Eric
AU  - Schüle, Roland
AU  - Bechtel-Walz, Wibke
AU  - Huber, Tobias B
TI  - Lysine-specific histone demethylase 1a regulates nephron development and long-term transcriptional programming.
JO  - JCI insight
VL  - 11
IS  - 5
SN  - 2379-3708
CY  - Ann Arbor, Michigan
PB  - JCI Insight
M1  - DKFZ-2026-00555
SP  - e190283
PY  - 2026
AB  - 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.
KW  - Animals
KW  - Nephrons: growth & development
KW  - Nephrons: metabolism
KW  - Nephrons: pathology
KW  - Mice
KW  - Mice, Knockout
KW  - Histone Demethylases: genetics
KW  - Histone Demethylases: metabolism
KW  - Humans
KW  - Podocytes: metabolism
KW  - Cell Differentiation: genetics
KW  - Cell Proliferation: genetics
KW  - Gene Expression Regulation, Developmental
KW  - Male
KW  - Epigenesis, Genetic
KW  - Organoids
KW  - Chronic kidney disease (Other)
KW  - Development (Other)
KW  - Epigenetics (Other)
KW  - Nephrology (Other)
KW  - KDM1a protein, mouse (NLM Chemicals)
KW  - Histone Demethylases (NLM Chemicals)
KW  - KDM1A protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41797715
DO  - DOI:10.1172/jci.insight.190283
UR  - https://inrepo02.dkfz.de/record/310355
ER  -