Lysine-specific histone demethylase 1a regulates nephron development and long-term transcriptional programming
收藏University of Hamburg2027-01-01 更新2026-04-17 收录
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资源简介：
Low nephron endowment constitutes a risk factor for hypertension and renal disease. Epigenetic regulation is crucial for nephron progenitor cell differentiation, impacting nephron number and renal function. The role of many epigenetic modulators, such as Lysine-specific histone demethylase 1a (LSD1), remains unclear. We used <em>Lsd1</em> knockout mice to demonstrate that <em>Lsd1</em> depletion in nephron progenitor cells results in reduced kidney size in neonates and leads to glomerulosclerosis, proteinuria, and renal cysts in adults. Notably, LSD1 deletion in podocytes or tubular cells did not replicate these effects. CRISPR/Cas9-mediated <em>LSD1</em> 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 non-coding RNAs indicates roles in cell proliferation. Our study reveals the critical role of LSD1 function in nephron development and highlights its impact on transcriptional programming for long-term renal function and susceptibility to cyst formation.
提供机构：
5Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 2Hamburg Center for Kidney Health, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
创建时间：
2027-01-01
