Adult pancreatic islet endocrine cells emerge as fetal hormone-expressing cells

Marta Perez-Frances, Maria Valentina Abate, Delphine Baronnier, Philipp E. Scherer, Yoshio Fujitani, Fabrizio Thorel, Pedro L. Herrera

Research output: Contribution to journalArticlepeer-review

Abstract

The precise developmental dynamics of the pancreatic islet endocrine cell types, and their interrelation, are unknown. Some authors claim the persistence of islet cell differentiation from precursor cells after birth (“neogenesis”). Here, using four conditional cell lineage tracing (“pulse-and-chase”) murine models, we describe the natural history of pancreatic islet cells, once they express a hormone gene, until late in life. Concerning the contribution of early-appearing embryonic hormone-expressing cells to the formation of islets, we report that adult islet cells emerge from embryonic hormone-expressing cells arising at different time points during development, without any evidence of postnatal neogenesis. We observe specific patterns of hormone gene activation and switching during islet morphogenesis, revealing that, within each cell type, cells have heterogeneous developmental trajectories. This likely applies to most maturating cells in the body, and explains the observed phenotypic variability within differentiated cell types. Such knowledge should help devising novel regenerative therapies.

Original languageEnglish (US)
Article number110377
JournalCell Reports
Volume38
Issue number7
DOIs
StatePublished - Feb 15 2022

Keywords

  • CRISPR
  • cell lineage tracing
  • development
  • diabetes
  • hormone
  • insulin gene expression
  • islet
  • pancreas
  • pulse-and-chase
  • transgenic mouse

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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