Sign-up for our newsletter
Protocols & Methods
Reagents & Resources
IMPC / KOMP Data
Research Assistant Professor
Tulane University Health Sciences Center Campus
p53-Regulated Metabolic Fitness of Self-Renewing Nephron Progenitor Cells
Nearly 3-10% of all pregnancies are affected by abnormal glucose regulation. Infants of diabetic mothers (IDM) are at a four-fold higher risk for congenital malformations of kidneys, brain and heart, as well as antenatal, perinatal or neonatal morbidity. Renal defects include hypoplasia with a significant nephron deficit, agenesis, cystic kidneys, ureteral duplication and hydronephrosis. Congenital low nephron number is a common cause of pediatric renal failure, adult-onset hypertension and chronic kidney disease - all clinically significant diseases without a cure. Availability of nephron progenitor cells (NPC) and their efficient differentiation into nephrons are major determinants of nephron endowment. The Cited1+/Six2+ sub-compartment of the cap mesenchyme is the stem cell niche, and marks the definitive self-renewing NPC. A self-renewal defect would result in a loss of these cells and consequently a diminished progenitor pool. A fundamental question is what regulates the stemness of NPCs. In a conditional knock-out model of the transcription factor p53 from the nephron progenitor cells, we observed progressive and selective depletion of self-renewing progenitors, nephron deficit and adult-onset hypertension. RNA-Seq data indicate that top down-regulated genes regulate energy metabolism pathways. Preliminary mechanistic studies demonstrate decreased ATP and ROS levels in Six2p53-/- cells. Balanced ATP and biomass synthesis (nucleotides, amino acids etc.) via oxidative phosphorylation (Oxphos) and glycolysis, respectively, are critical drivers of self-renewal and proliferation. Cell competition studies in Drosophila implicate p53 as a sensor and key modulator of adaptive metabolic changes to maintain cell viability. Based on these data we hypothesize that p53 enables self-renewal of the NPC by maintaining metabolic homeostasis in response to niche cues. Our long-term goal is to define the role of p53 in integrating niche signals (nutrient, growth factors, variations in oxygen tension) with key sensory pathways (AMPK, mTOR, Hif1a). For this pilot study we propose to establish the metabolic profile of Cited1+/Six2+ cells, which is currently unknown, under normal, high and low glucose conditions, and evaluate Cited1+/Six2+ NPC cell fate after a metabolic switch (by pharmacological inhibition of glycolysis or Oxphos.
Drag a column header and drop it here to group by that column
p53-Regulated Metabolic Fitness of Self-Renewing Nephron Progenitor Cells (Saifudeen, Zubaida)
View Progress Report Document
No uploaded documents found.
Year: 2015; Items: 1
p53 Enables metabolic fitness and self-renewal of nephron progenitor cells.
Li Y, Liu J, Li W, Brown A, Baddoo M, Li M, Carroll T, Oxburgh L, Feng Y, Saifudeen Z
Development (Cambridge, England)
, 2015 (142), 1228 - 41
No uploaded documents found.
No protocols found.
The DiaComp Steering Committee is the governing body of the consortium. The principle function of this committee is to guide the scientific direction of the consortium. This is accomplished by creating various subcommittees necessary to advance the scientific goals and providing guidance to the broader complications research community. Policies for the consortium are developed through consultation with the
External Evaluation Committee
The DiaComp Nephropathy Committee has the principal function of furthering the mission of the consortium with regard to diabetic kidney disease.
Curation Flag Information
New comment to be added:
No records to display.
Welcome to the DiaComp Login / Account Request Page.
Note: Passwords are case-sensitive.
Please save my Email Address on this machine.
Not a member?
If you are a funded DiaComp investigator, a member of an investigator's lab,
or an External Scientific Panel member to the consortium, please
request an account.
Forgot your password?
Enter your Email Address and
There was a problem with the page:
Safari Browser Detected...
We strive to make the DiaComp site compatable with as many browsers as possible, but some of our third party tools don't work with the Safari browser.
In order to explore this site we highly recommend using the most recent versions of the following browsers:
© 2018 DiaComp.org
All rights reserved
Please acknowledge all posters, manuscripts or scientific materials that were generated in part or whole using funds from the Diabetic Complications Consortium(DiaComp) using the following text:
Financial support for this work provided by the NIDDK Diabetic Complications Consortium (RRID:SCR_001415, www.diacomp.org), grants DK076169 and DK115255
Citation text and image have been copied to your clipboard. You may now paste them into your document. Thank you!