Development of the Human Pancreas From Foregut to Endocrine Commitment

• Published in: Diabetes (New York, N.Y.) Vol. 62; no. 10; pp. 3514 - 3522
• Main Authors: JENNINGS, Rachel E, BERRY, Andrew A, KIRKWOOD-WILSON, Rebecca, ROBERTS, Neil A, HEARN, Thomas, SALISBURY, Rachel J, BLAYLOCK, Jennifer, HANLEY, Karen Piper, HANLEY, Neil A
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01-10-2013
• Subjects: Analysis; Animals; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - metabolism; Biological and medical sciences; Cell Differentiation; Cell Lineage; Diabetes. Impaired glucose tolerance; Endocrine cells; Endocrine pancreas. Apud cells (diseases); Endocrine system; Endocrine System - embryology; Endocrine System - growth & development; Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Gene Expression Regulation, Developmental; Homeobox Protein Nkx-2.2; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Humans; Immunohistochemistry; Insulin-Secreting Cells; Medical sciences; Mice; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Nuclear Proteins; Original Research; Pancreas; Pancreas - embryology; Pancreas - growth & development; Pregnancy; Stem cell research; Stem cells; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; Zebrafish Proteins; Endocrinopathy; Human; Development; Pancreas; Diabetes mellitus
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db12-1479

Knowledge of human pancreas development underpins our interpretation and exploitation of human pluripotent stem cell (PSC) differentiation toward a β-cell fate. However, almost no information exists on the early events of human pancreatic specification in the distal foregut, bud formation, and early development. Here, we have studied the expression profiles of key lineage-specific markers to understand differentiation and morphogenetic events during human pancreas development. The notochord was adjacent to the dorsal foregut endoderm during the fourth week of development before pancreatic duodenal homeobox-1 detection. In contrast to the published data from mouse embryos, during human pancreas development, we detected only a single-phase of Neurogenin 3 (NEUROG3) expression and endocrine differentiation from approximately 8 weeks, before which Nirenberg and Kim homeobox 2.2 (NKX2.2) was not observed in the pancreatic progenitor cell population. In addition to revealing a number of disparities in timing between human and mouse development, these data, directly assembled from human tissue, allow combinations of transcription factors to define sequential stages and differentiating pancreatic cell types. The data are anticipated to provide a useful reference point for stem cell researchers looking to differentiate human PSCs in vitro toward the pancreatic β-cell so as to model human development or enable drug discovery and potential cell therapy.