# Genetic and physiologic regulation of pig islet development and function

> **NIH NIH R01** · STANFORD UNIVERSITY · 2022 · $649,675

## Abstract

Abstract
 Studies in rodents have fundamentally advanced our understanding of pancreatic islet cell
development and function, but limitations of rodent models for understanding human pancreas
formation and disease have intensified interest in experimental systems that more closely reflect
human pancreas development and islet function. Our studies have revealed advantages for
investigating islet development in pigs, including evidence for multiple conserved features of
islet development in pigs and humans, not observed in mice. This includes expression of
transcription factors like SIX2 and SIX3 which govern hallmark features of human islet β cell fate
and function. We have developed a reliable framework for procuring pig pancreata and islets
from any developmental stage, and described molecular, cellular, signaling and genetic features
of developing pig α, β, and δ cells from fetal to neo-natal stages, including the first detailed
developmental transcriptome of these cells. In addition, our team has generated some of the
first gene-edited pigs using CRISPR/Cas9 targeting. These advances motivate the following
Aims:
Aim 1. Elucidate the genetic architecture of pig islet cell development and functional maturation
Aim 2. Identify native regulators of pig islet SIX2 and SIX3 expression
Aim 3. Investigate phenotypes of HNF1A heterozygous mutation in pigs
To achieve our aims, we assembled a superb team of collaborating investigators with
complementary expertise in developmental biology, pig genetics, islet biology, genomics and
diabetes research. This work should allow previously unattainable investigation of genetic and
physiological mechanisms regulating pig islet cells. This includes identification of regulatory
features that connect chromatin dynamics and gene transcription to control islet α, β and δ cell
fate and function, and creation of new models of MODY that better recapitulate human disease
genetics, pathogenesis and therapeutics. Our work should create new flexible experimental
paradigms to investigate development and functional maturation of islet cells from physiological
and pathological stages, a striking advantage that broadens the impact of our proposal on
human health.

## Key facts

- **NIH application ID:** 10414985
- **Project number:** 5R01DK128932-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Trish Berger
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $649,675
- **Award type:** 5
- **Project period:** 2021-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10414985

## Citation

> US National Institutes of Health, RePORTER application 10414985, Genetic and physiologic regulation of pig islet development and function (5R01DK128932-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10414985. Licensed CC0.

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