# Cell Interactions in Development of the Mammalian Kidney

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $669,951

## Abstract

Project Summary / Abstract
Approximately 1,000,000 Americans have end state renal disease and these numbers are increasing. Dialysis
provides an essential but unsatisfactory palliative solution with high morbidity and high mortality. A kidney
transplant can restore kidney function, but the number of transplants is insufficient for the patient population, and
the numbers have not increased significantly over the last 20 years. Several groups have demonstrated the
directed differentiation of kidney-like structures, kidney organoids, from mouse and human pluripotent stem cells.
These advances highlight the need to generate an enhanced understanding of the critical processes underlying
mammalian nephrogenic programs. Further, recent advances in our understanding of human kidney
development from the McMahon group emphasize the importance of direct human studies. Consequently, we
combine analysis across developing mouse and human kidney systems with human kidney organoids to
examine key regulatory processes in the nephrogenic program. In Specific Aim 1, we will determine the
epigenetic control mechanisms regulating normal mouse and human nephron progenitor states through
extensive analysis of RNA-seq, ChIP-seq, ATAC-seq and HI-C datasets. The regulatory processes identified
through these studies are interesting in their own right but serve also as a critical benchmark for in vitro efforts
to generate normal nephron progenitor cells. In Specific Aim 2, we will determine the transcriptional
mechanisms of Wnt/ß-catenin pathway mediated maintenance and commitment of nephron progenitor
cells. Wnt signaling plays a central role in stem/progenitor regulation in a variety of organ systems. Recent
advances in nephron progenitor culture and differentiation make the kidney an attractive model for unravelling
the duality of Wnt pathway action on nephron progenitor cells. In Specific Aim 3, we will examine the role of
canonical Wnt signaling in distal patterning of the developing nephron. In patterning the early nephron
anlagen, several lines of evidence links Notch and Wnt signaling to proximal and distal fate-specification,
respectively. We will examine the role of Wnt-signaling in distal development using human and optimized human
pluripotent cell kidney organoid model system, genetically engineered to report on nephron patterning events.
The anticipated research outcomes will identify critical regulatory mechanisms governing the maintenance,
commitment and differentiation of stem/progenitor cell types of broad interest to researchers working across
different organ systems. The studies will also enhance our understanding of human kidney development and
educate effective therapeutic application of stem cell-derived kidney structures.

## Key facts

- **NIH application ID:** 9849765
- **Project number:** 5R01DK054364-22
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** ANDREW P. MCMAHON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $669,951
- **Award type:** 5
- **Project period:** 1998-09-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9849765

## Citation

> US National Institutes of Health, RePORTER application 9849765, Cell Interactions in Development of the Mammalian Kidney (5R01DK054364-22). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9849765. Licensed CC0.

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