Validating expression of beta cell maturation-associated genes in human pancreas development

Area of Science:

• Endocrinology
• Developmental Biology
• Stem Cell Biology

Background:

• Identifying markers for human pancreatic beta cell maturation is crucial for understanding islet development and improving stem cell-derived islet (SC-islet) differentiation.
• Existing markers often rely on animal models or SC-islets, necessitating validation in human systems.

Purpose of the Study:

• To identify reliable gene markers for human pancreatic beta cell maturation.
• To evaluate Urocortin-3 (UCN3) as a maturation marker and discover novel markers.

Main Methods:

• Analysis of gene expression in human fetal islets and stem cell-derived islets (SC-islets).
• Assessment of functional maturation (glucose-stimulated insulin secretion) in SC-islets.
• Screening of candidate maturation-associated genes using human tissue banks and SC-islet resources.

Main Results:

• Urocortin-3 (UCN3) expression in human fetal islets precedes functional maturation and does not correlate with it in SC-islets.
• CHGB, G6PC2, FAM159B, GLUT1, IAPP, and ENTPD3 were identified as markers whose expression correlates with the onset of functional maturation in human beta cells.
• ERO1LB, HDAC9, KLF9, and ZNT8 showed no significant expression change between fetal and adult human beta cells.

Conclusions:

• UCN3 is not a reliable marker for functional human beta cell maturation.
• Several novel genes (CHGB, G6PC2, FAM159B, GLUT1, IAPP, ENTPD3) are identified as key developmental markers for human beta cell maturation.
• These markers can aid in understanding human islet development and refining SC-islet differentiation protocols.