ArticleDevelopment (Cambridge, England)2015
p53 Enables metabolic fitness and self-renewal of nephron progenitor cells.
Article in Development (Cambridge, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 38 citations in OpenAlex.
- The Impact of Low-Protein Diet on the Molecular and Cellular Development of the Fetal Kidney.Journal of the American Society of Nephrology : JASN · 2026Article
- Epigenetic regulation of nephrogenesis: from Waddington's landscape to adult disease.American journal of physiology. Renal physiology · 2026Review
- Single cell transcription revealing key transcription factors in embryonic kidney development.Molecular and cellular biochemistry · 2025Article
- Energy depletion by cell proliferation sensitizes the kidney epithelial cells to injury.American journal of physiology. Renal physiology · 2024Article
- Acetyl-CoA is a key molecule for nephron progenitor cell pool maintenance.Nature communications · 2023Article
- Omics profiling identifies the regulatory functions of the MAPK/ERK pathway in nephron progenitor metabolism.Development (Cambridge, England) · 2022Article
- The Senescence Markers p16INK4A, p14ARF/p19ARF, and p21 in Organ Development and Homeostasis.Cells · 2022Review
- Comparative whole-genome transcriptome analysis in renal cell populations reveals high tissue specificity of MAPK/ERK targets in embryonic kidney.BMC biology · 2022Article
- Tubule-specific deletion ofMolecular therapy. Nucleic acids · 2021Article
- Single-cell RNA sequencing reveals differential cell cycle activity in key cell populations during nephrogenesis.Scientific reports · 2021Article
- ER stress-induced modulation of neural activity and seizure susceptibility is impaired in a fragile X syndrome mouse model.Neurobiology of disease · 2021Article
- Metabolic programming of nephron progenitor cell fate.Pediatric nephrology (Berlin, Germany) · 2021Review
- Metabolic requirements of the nephron.Pediatric nephrology (Berlin, Germany) · 2020Review
- Von Hippel-Lindau Acts as a Metabolic Switch Controlling Nephron Progenitor Differentiation.Journal of the American Society of Nephrology : JASN · 2019Article
- MAPK/ERK Signaling in Regulation of Renal Differentiation.International journal of molecular sciences · 2019Review
- Conserved and Divergent Features of Mesenchymal Progenitor Cell Types within the Cortical Nephrogenic Niche of the Human and Mouse Kidney.Journal of the American Society of Nephrology : JASN · 2018Article
- Regulation of Nephron Progenitor Cell Self-Renewal by Intermediary Metabolism.Journal of the American Society of Nephrology : JASN · 2017Article
- Increased Arf/p53 activity in stem cells, aging and cancer.Aging cell · 2017Review
- Regulation of kidney development by the Mdm2/Mdm4-p53 axis.Journal of molecular cell biology · 2017Review
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 1 country.
Funding
Abstract
Contrary to its classic role in restraining cell proliferation, we demonstrate here a divergent function of p53 in the maintenance of self-renewal of the nephron progenitor pool in the embryonic mouse kidney. Nephron endowment is regulated by progenitor availability and differentiation potential. Conditional deletion of p53 in nephron progenitor cells (Six2Cre(+);p53(fl/fl)) induces progressive depletion of Cited1(+)/Six2(+) self-renewing progenitors and loss of cap mesenchyme (CM) integrity. The Six2(p53-null) CM is disorganized, with interspersed stromal cells and an absence of a distinct CM-epithelia and CM-stroma interface. Impaired cell adhesion and epithelialization are indicated by decreased E-cadherin and NCAM expression and by ineffective differentiation in response to Wnt induction. The Six2Cre(+);p53(fl/fl) cap has 30% fewer Six2(GFP(+)) cells. Apoptotic index is unchanged, whereas proliferation index is significantly reduced in accordance with cell cycle analysis showing disproportionately fewer Six2Cre(+);p53(fl/fl) cells in the S and G2/M phases compared with Six2Cre(+);p53(+/+) cells. Mutant kidneys are hypoplastic with fewer generations of nascent nephrons. A significant increase in mean arterial pressure is observed in early adulthood in both germline and conditional Six2(p53-null) mice, linking p53-mediated defects in kidney development to hypertension. RNA-Seq analyses of FACS-isolated wild-type and Six2(GFP(+)) CM cells revealed that the top downregulated genes in Six2Cre(+);p53(fl/fl) CM belong to glucose metabolism and adhesion and/or migration pathways. Mutant cells exhibit a ∼ 50% decrease in ATP levels and a 30% decrease in levels of reactive oxygen species, indicating energy metabolism dysfunction. In summary, our data indicate a novel role for p53 in enabling the metabolic fitness and self-renewal of nephron progenitors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.