# Microenvironmental cues control pancreas cell fate and beta-cell maturation

> **NIH NIH R01** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2020 · $408,208

## Abstract

ABSTRACT
Current strategies for treating type 1 diabetes via cell replacement are limited by a
shortage of donor islets; human pluripotent stem cell (hPSC)-derived β (hPSC-β) cells
represent a promising solution to this dilemma. To improve current methodologies for the
differentiation of hPSCs towards functional β-cells, a comprehensive understanding of
the molecular programs for the processes of endocrine development and β-cells
maturation is still required. Our preliminary studies suggested that integrin signaling and
microenvironment stiffness play an integral role in coordinating islet and β-cell
development. The present proposal seeks to elucidate the role that integrin and
microenvironment stiffness play in coordinating these complex processes. We aim to
uncover the mechanisms of integrin signaling in controlling 1) endocrine cell fate
decision, 2) islet development, and 3) β-cell maturation. We will utilize a combination of
pancreas-, islet-, and β-cell-specific deletion mouse models to inactivate integrin subunit
β1 (Itgb1, a subunit essential for integrin signaling). We also aim to promote in vitro
maturation of hPSC-β cells by controlling the microenvironments stiffness. To achieve
this, we established a novel cell culture platform for temporal control of
microenvironment stiffness. By culturing and differentiating the hPSC-β progenitors on
this platform, we will elucidate the role which microenvironment stiffness plays on β-cell
maturation. Together, our study will provide a greater understanding of the role of
integrin signaling and microenvironment stiffness in regulating β-cell development. This
will inform future functional hPSC-β generation strategies.

## Key facts

- **NIH application ID:** 9980903
- **Project number:** 5R01DK119590-03
- **Recipient organization:** BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
- **Principal Investigator:** Hung-Ping Shih
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $408,208
- **Award type:** 5
- **Project period:** 2018-09-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980903

## Citation

> US National Institutes of Health, RePORTER application 9980903, Microenvironmental cues control pancreas cell fate and beta-cell maturation (5R01DK119590-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9980903. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*