ArticleKidney international2018
Haploinsufficiency for the Six2 gene increases nephron progenitor proliferation promoting branching and nephron number.
Article in Kidney international, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Gestational Ketosis Compromises Nephron Endowment and Long-Term Kidney Function in Offspring.Journal of the American Society of Nephrology : JASN · 2026Article
- Dose-Dependent and Non-Autonomous Signaling in CAKUT: A Lineage-Specific Framework from Conditional Knockout Studies.Biomolecules · 2026Review
- Maternal nutrition can rapidly rescue a nephron deficit in low birthweight offspring.npj metabolic health and disease · 2025Article
- Expression of ENL YEATS domain tumor mutations in nephrogenic or stromal lineage impairs kidney development.Nature communications · 2025Article
- A guide to studying 3D genome structure and dynamics in the kidney.Nature reviews. Nephrology · 2025Review
- A biomimetic branching signal-passing tile assembly model with dynamic growth and disassembly.Journal of the Royal Society, Interface · 2024Article
- SIX2 promotes cell plasticity via Wnt/β-catenin signalling in androgen receptor independent prostate cancer.Nucleic acids research · 2024Article
- Human pluripotent stem cell-derived kidney organoids: Current progress and challenges.World journal of stem cells · 2024Review
- Regulation of nephron progenitor cell lifespan and nephron endowment.Nature reviews. Nephrology · 2022Review
- Progenitor translatome changes coordinated by Tsc1 increase perception of Wnt signals to end nephrogenesis.Nature communications · 2021Article
- Vascular deficiencies in renal organoids and ex vivo kidney organogenesis.Developmental biology · 2021Article
- Review
- ADAM10 mediates ectopic proximal tubule development and renal fibrosis through Notch signalling.The Journal of pathology · 2020Article
- Generation and characterization of Six2 conditional mice.Genesis (New York, N.Y. : 2000) · 2020Article
- Advances in our understanding of genetic kidney disease using kidney organoids.Pediatric nephrology (Berlin, Germany) · 2020Review
- The FGF, TGFβ and WNT axis Modulate Self-renewal of Human SIX2Scientific reports · 2020Article
- Transcription factor Six2 induces a stem cell-like phenotype in renal cell carcinoma cells.FEBS open bio · 2019Article
- Transcriptional factor six2 promotes the competitive endogenous RNA network between CYP4Z1 and pseudogene CYP4Z2P responsible for maintaining the stemness of breast cancer cells.Journal of hematology & oncology · 2019Article
- Single-cell transcriptomics reveals gene expression dynamics of human fetal kidney development.PLoS biology · 2019Article
- DNA Methyltransferase 1 Controls Nephron Progenitor Cell Renewal and Differentiation.Journal of the American Society of Nephrology : JASN · 2019Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
The regulation of final nephron number in the kidney is poorly understood. Cessation of nephron formation occurs when the self-renewing nephron progenitor population commits to differentiation. Transcription factors within this progenitor population, such as SIX2, are assumed to control expression of genes promoting self-renewal such that homozygous Six2 deletion results in premature commitment and an early halt to kidney development. In contrast, Six2 heterozygotes were assumed to be unaffected. Using quantitative morphometry, we found a paradoxical 18% increase in ureteric branching and final nephron number in Six2 heterozygotes, despite evidence for reduced levels of SIX2 protein and transcript. This was accompanied by a clear shift in nephron progenitor identity with a distinct subset of downregulated progenitor genes such as Cited1 and Meox1 while other genes were unaffected. The net result was an increase in nephron progenitor proliferation, as assessed by elevated EdU (5-ethynyl-2'-deoxyuridine) labeling, an increase in MYC protein, and transcriptional upregulation of MYC target genes. Heterozygosity for Six2 on an Fgf20-/- background resulted in premature differentiation of the progenitor population, confirming that progenitor regulation is compromised in Six2 heterozygotes. Overall, our studies reveal a unique dose response of nephron progenitors to the level of SIX2 protein in which the role of SIX2 in progenitor proliferation versus self-renewal is separable.
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Registered trials
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