Imaging Human Pancreatic Endocrinogenesis During Early Prenatal Life.

Area of Science:

• Developmental Biology
• Endocrinology
• Cell Biology

Background:

• Human pancreas development data is limited, often relying on 2D staining.
• Previous studies focused on murine models, leaving gaps in human endocrinogenesis understanding.

Purpose of the Study:

• To investigate human pancreatic endocrinogenesis during the first trimester.
• To characterize the spatiotemporal dynamics and clustering of endocrine cells in early human pancreases.
• To compare human islet formation with rodent models.

Main Methods:

• Collection of human embryonic and fetal pancreases (first trimester).
• Application of in toto staining, tissue clearing, and light-sheet fluorescence microscopy.
• Analysis of endocrine cell emergence, distribution, and islet morphology.

Main Results:

• Insulin-, glucagon-, and somatostatin-positive cells appear simultaneously at Carnegie stage 16.
• Bihormonal cells were detected in early human pancreases (CS16-CS18) but not later.
• Human fetal islets show a core-mantle structure (β-cells core, α/δ-cells mantle), differing from adult human islets.
• Fetal islet size and structure suggest adult islet formation via fusion, contrasting with mouse islet fission.

Conclusions:

• Human pancreatic endocrinogenesis exhibits distinct features compared to rodents, with simultaneous endocrine cell differentiation.
• Early human islet development may involve cell fusion, proposing a novel mechanism for adult islet formation.
• This study provides a comprehensive spatiotemporal map of human pancreatic endocrinogenesis.