Journal Article

DKFZ-2026-00555

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Lysine-specific histone demethylase 1a regulates nephron development and long-term transcriptional programming.

Wanner, N. ; Keller, J. ; Liaukouskaya, N. ; Andrieux, G. ; Laufer, S. D. ; Rogg, M. ; Bork, T. ; Liang, W. ; Braun, F. ; Haas, F. ; Wong, M. N. ; Puelles, V. G. ; Gies, S. E. ; Meyer, C. ; Boerries, M.DKFZ* ; Helmstädter, M. ; Kretz, O. ; Hild, I. ; Metzger, E.DKFZ* ; Schüle, R. ; Bechtel-Walz, W. ; Huber, T. B.

2026
JCI Insight Ann Arbor, Michigan

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.

Keyword(s): Animals (MeSH) ; Nephrons: growth & development (MeSH) ; Nephrons: metabolism (MeSH) ; Nephrons: pathology (MeSH) ; Mice (MeSH) ; Mice, Knockout (MeSH) ; Histone Demethylases: genetics (MeSH) ; Histone Demethylases: metabolism (MeSH) ; Humans (MeSH) ; Podocytes: metabolism (MeSH) ; Cell Differentiation: genetics (MeSH) ; Cell Proliferation: genetics (MeSH) ; Gene Expression Regulation, Developmental (MeSH) ; Male (MeSH) ; Epigenesis, Genetic (MeSH) ; Organoids (MeSH) ; Chronic kidney disease ; Development ; Epigenetics ; Nephrology ; KDM1a protein, mouse ; Histone Demethylases ; KDM1A protein, human

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Freiburg (FR01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2026

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Database coverage:
; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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