# Diversity-generating mechanisms for mammalian intercalated cell lineages

> **NIH NIH F31** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2022 · $46,753

## Abstract

Project Summary/Abstract
Three-quarters of a million Americans have End Stage Renal Disease (ESRD). Their only treatment options are
dialysis, with poor long term survival prospects, or a curative kidney transplant, with too few kidneys to meet
patient need. One way to address the shortage of transplantable kidneys is to develop a thorough insight into
essential cell types and how they are generated, and then to use this insight to generate functional, cell-based
kidney replacements. The physiologically relevant epithelial networks of the kidney arise from two distinct
progenitor populations. Nephron progenitors generate the nephrons, of which there are approximately one million
in the human kidney, and adjacent ureteric progenitors generate the branched network to the collecting system,
to which nephrons connect. Homeostasis is maintained by specialized cell types in both the nephron and the
collecting duct. Notably, water and salt, and pH balance, are regulated by principal cells (PCs) and intercalated
cells (ICs), respectively. There are three subtypes of intercalated cells: type A intercalated cells (A-ICs), type B
intercalated cells (B-ICs) and non-A-non-B intercalated cells that perform distinct functions in the regulation of
pH homeostasis. Interestingly, the McMahon group recently demonstrated both PCs and ICs have dual origins
from both nephron and ureteric progenitor cells, an unusual developmental process. Here, I aim to identify the
mechanisms generating similar, but not identical, IC subtypes from distinct kidney progenitor populations. In
Specific Aim 1, I will focus on identifying the targets of transcription factors that are known to be essential for
the development of ICs: Tfcp2l1 and Foxi1. I will also profile the targets of transcription factors that have not yet
been described in ICs: Dmrt2 distinguishes both nephron and ureteric epithelial derived IC-A cell types from
Hmx2/Hmx3 expressing IC-B cell types. Differential Hmx gene expression sub-divides the IC-B populations:
Hmx2+ B-ICs and non-A-nonB ICs are nephron-derived and Hmx2+/Hmx3+ B-ICs are ureteric lineage derived.
We hypothesize that Tfcp2l1 and Foxi1 initiate a general IC developmental program, while Dmrt2, Hmx2, and
Hmx3 have mutually repressive actions in the generation of IC subtypes. I will use biochemical approaches and
generate tagged alleles to identify regulatory interactions for these transcription factors within ICs of both
lineages. In Specific Aim 2, I will use genetic approaches in vivo and a ureteric organoid model to determine
the requirement of these factors in the functional transcriptional interplay generating mammalian ICs. Taken
together, this proposed work will define a regulatory framework for the development of intercalated cells within
the ureteric and nephron lineages in the kidney and provide new insights into the regulatory programs governing
cell types involved in mammalian kidney function.

## Key facts

- **NIH application ID:** 10466348
- **Project number:** 1F31DK130597-01A1
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Riana Kin Parvez
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,753
- **Award type:** 1
- **Project period:** 2022-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10466348

## Citation

> US National Institutes of Health, RePORTER application 10466348, Diversity-generating mechanisms for mammalian intercalated cell lineages (1F31DK130597-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10466348. Licensed CC0.

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