Retinoic acid promotes the generation of pancreatic endocrine progenitor cells and their further differentiation into β-cells

Maria Öström, Kelly A. Loffler, Sara Edfalk, Lars Selander, Ulf Dahl, Camillo Ricordi, Jongmin Jeon, Mayrin Correa-Medina, Juan Diez, Helena Edlund

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

The identification of secreted factors that can selectively stimulate the generation of insulin producing β-cells from stem and/or progenitor cells represent a significant step in the development of stem cell-based β-cell replacement therapy. By elucidating the molecular mechanisms that regulate the generation of β-cells during normal pancreatic development such putative factors may be identified. In the mouse, β-cells increase markedly in numbers from embryonic day (e) 14.5 and onwards, but the extra-cellular signal(s) that promotes the selective generation of β-cells at these stages remains to be identified. Here we show that the retinoic acid (RA) synthesizing enzyme Raldh1 is expressed in developing mouse and human pancreas at stages when β-cells are generated. We also provide evidence that RA induces the generation of Ngn3- endocrine progenitor cells and stimulates their further differentiation into β-cells by activating a program of cell differentiation that recapitulates the normal temporal program of β-cell differentiation.

Original languageEnglish (US)
Article numbere2841
JournalPloS one
Volume3
Issue number7
DOIs
StatePublished - Jul 30 2008

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Öström, M., Loffler, K. A., Edfalk, S., Selander, L., Dahl, U., Ricordi, C., Jeon, J., Correa-Medina, M., Diez, J., & Edlund, H. (2008). Retinoic acid promotes the generation of pancreatic endocrine progenitor cells and their further differentiation into β-cells. PloS one, 3(7), [e2841]. https://doi.org/10.1371/journal.pone.0002841