Endocrine Cell Clustering During Human Pancreas Development

2009/04/13 by Jongmin Jeon, Mayrin Correa-Medina, Camillo Ricordi +3 · 204 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #Biology #Cell biology #Cellular differentiation #Diabetes Management and Research #Diabetes and associated disorders #Embryonic stem cell #Endocrine system #Endocrinology #Enteroendocrine cell #Fetus #Gene expression #Genetics #Glucagon #Hormone #Immunohistochemistry #Immunology #Immunostaining #In situ hybridization #In vitro #Insulin #Internal medicine #Islet #Medicine #Pancreas #Pancreatic function and diabetes #Pregnancy #Progenitor cell #Stem cell

paper · open access · doi:10.1369/jhc.2009.953307

published in Journal of Histochemistry & Cytochemistry 57(9), 811-824 (SAGE Publishing)

openalex publication_date 2009/04/13 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/29

Abstract

The development of efficient, reproducible protocols for directed in vitro differentiation of human embryonic stem (hES) cells into insulin-producing beta cells will benefit greatly from increased knowledge regarding the spatiotemporal expression profile of key instructive factors involved in human endocrine cell generation. Human fetal pancreases 7 to 21 weeks of gestational age, were collected following consent immediately after pregnancy termination and processed for immunostaining, in situ hybridization, and real-time RT-PCR expression analyses. Islet-like structures appear from approximately week 12 and, unlike the mixed architecture observed in adult islets, fetal islets are initially formed predominantly by aggregated insulin- or glucagon-expressing cells. The period studied (7-22 weeks) coincides with a decrease in the proliferation and an increase in the differentiation of the progenitor cells, the initiation of NGN3 expression, and the appearance of differentiated endocrine cells. The present study provides a detailed characterization of islet formation and expression profiles of key intrinsic and extrinsic factors during human pancreas development. This information is beneficial for the development of efficient protocols that will allow guided in vitro differentiation of hES cells into insulin-producing cells.

Citations

• Assessment of Human Pancreatic Islet Architecture and Composition by Laser Scanning Confocal Microscopy

Cited by

• (Re)generating Human Beta Cells: Status, Pitfalls, and Perspectives
• Deconstructing pancreas development to reconstruct human islets from pluripotent stem cells. [europepmc]
• Pancreatic islet plasticity: interspecies comparison of islet architecture and composition. [europepmc]
• INS(GFP/w) human embryonic stem cells facilitate isolation of in vitro derived insulin-producing cells. [europepmc]
• Generation of beta cells from human pluripotent stem cells: Potential for regenerative medicine. [europepmc]
• Sympathetic innervation during development is necessary for pancreatic islet architecture and functional maturation. [europepmc]
• Initial cell seeding density influences pancreatic endocrine development during in vitro differentiation of human embryonic stem cells. [europepmc]
• Pancreas development in humans. [europepmc]
• Revealing transcription factors during human pancreatic β cell development. [europepmc]
• Primary cilia in pancreatic development and disease. [europepmc]
• Islet formation in mice and men: lessons for the generation of functional insulin-producing β-cells from human pluripotent stem cells. [europepmc]
• Structural similarities and differences between the human and the mouse pancreas. [europepmc]
• Pancreatic islet cell development and regeneration. [europepmc]
• Expressions of VEGF-A and VEGFR-2 in placentae from GDM pregnancies. [europepmc]
• PDX1, Neurogenin-3, and MAFA: critical transcription regulators for beta cell development and regeneration. [europepmc]
• Understanding human fetal pancreas development using subpopulation sorting, RNA sequencing and single-cell profiling. [europepmc]
• Recapitulating endocrine cell clustering in culture promotes maturation of human stem-cell-derived β cells. [europepmc]
• Endogenous Pancreatic β Cell Regeneration: A Potential Strategy for the Recovery of β Cell Deficiency in Diabetes. [europepmc]
• Alterations in Beta Cell Identity in Type 1 and Type 2 Diabetes. [europepmc]
• TGF-β Signaling in Pancreatic Islet β Cell Development and Function. [europepmc]
• Sequential progenitor states mark the generation of pancreatic endocrine lineages in mice and humans. [europepmc]
• Glucagon's Metabolic Action in Health and Disease. [europepmc]
• The Human Islet: Mini-Organ With Mega-Impact. [europepmc]
• A 3D system to model human pancreas development and its reference single-cell transcriptome atlas identify signaling pathways required for progenitor expansion. [europepmc]
• Functional, metabolic and transcriptional maturation of human pancreatic islets derived from stem cells. [europepmc]
• Deciphering early human pancreas development at the single-cell level. [europepmc]

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