Development of the human pancreas from foregut to endocrine commitment

Diabetes. 2013 Oct;62(10):3514-22. doi: 10.2337/db12-1479. Epub 2013 Apr 29.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Cell Differentiation*
  • Cell Lineage
  • Endocrine System / embryology
  • Endocrine System / growth & development
  • Female
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Immunohistochemistry
  • Insulin-Secreting Cells
  • Mice
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Pancreas / embryology*
  • Pancreas / growth & development*
  • Pregnancy
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Zebrafish Proteins

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Homeodomain Proteins
  • NEUROG3 protein, human
  • Nerve Tissue Proteins
  • Neurog3 protein, mouse
  • Nkx2.2 protein
  • Transcription Factors
  • Zebrafish Proteins