Related Experiment Video
Updated: May 5, 2026
08:32
Efficient Generation of Pancreas/Duodenum Homeobox Protein 1+ Posterior Foregut/Pancreatic Progenitors from hPSCs in Adhesion Cultures
Published on: March 27, 2019
6.0K
RFX3 is essential for the generation of functional human pancreatic islets from stem cells
Bushra Memon1, Noura Aldous1,2,3, Ahmed K Elsayed2,3
1Diabetes Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha, Qatar.
Diabetologia
|April 22, 2025
Summary
Regulatory factor X 3 (RFX3) is crucial for human pancreatic islet development, regulating cell differentiation and insulin secretion. Loss of RFX3 impairs islet function and promotes enterochromaffin cell growth, impacting diabetes susceptibility.
Area of Science:
- * Stem cell biology and developmental biology.
- * Endocrinology and metabolic research.
- * Molecular genetics and epigenetics.
Background:
- * The role of regulatory factor X 3 (RFX3) in human pancreatic islet development remains unexplored.
- * Induced pluripotent stem cells (iPSCs) offer a model for studying human islet organogenesis.
- * Understanding RFX3's function is key to advancing islet biology and diabetes research.
Purpose of the Study:
- * To investigate the function of RFX3 in human pancreatic islet development.
- * To determine if RFX3 regulates human islet cell differentiation using iPSC-derived organoids.
- * To explore the impact of RFX3 on beta cell function and insulin secretion.
Main Methods:
- * Generation of RFX3 knockout (RFX3 KO) iPSC lines via CRISPR/Cas9.
- * Differentiation of iPSCs into pancreatic islet organoids.
- * Assessment of gene expression, cell markers, apoptosis, proliferation, and glucose-stimulated insulin secretion.
- * Analysis of single-cell and bulk RNA-seq data to evaluate transcriptomic changes.
- * RFX3 overexpression to rescue gene expression dysregulation.
Main Results:
- * RFX3 is highly expressed in pancreatic progenitors, endocrine progenitors, and mature islet cells.
- * RFX3 loss disrupts endocrine gene regulation, reduces hormone-secreting cells, and impairs beta cell function and insulin secretion.
- * RFX3 deficiency leads to increased enterochromaffin cell abundance, smaller islet organoids, elevated thioredoxin-interacting protein, and increased apoptosis.
- * RFX3 overexpression successfully rescued dysregulated gene expression in RFX3 KO cells.
Conclusions:
- * RFX3 plays a critical role in regulating human islet cell differentiation.
- * RFX3 suppresses enterochromaffin cell specification during islet development.
- * Dysregulation of RFX3 impacts islet biology and may influence diabetes susceptibility.
