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

64 Citations (Scopus)

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
Article numbere2841
JournalPLoS One
Volume3
Issue number7
DOIs
StatePublished - Jul 30 2008

Fingerprint

Endocrine Cells
retinoic acid
Tretinoin
cell differentiation
stem cells
Cell Differentiation
Stem Cells
Stem cells
cells
Insulin
Enzymes
Cell- and Tissue-Based Therapy
mice
Pancreas
pancreas
insulin
therapeutics
stems
enzymes

ASJC Scopus subject areas

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

Cite this

Retinoic acid promotes the generation of pancreatic endocrine progenitor cells and their further differentiation into β-cells. / Öström, Maria; Loffler, Kelly A.; Edfalk, Sara; Selander, Lars; Dahl, Ulf; Ricordi, Camillo; Jeon, Jongmin; Correa-Medina, Mayrin; Diez, Juan; Edlund, Helena.

In: PLoS One, Vol. 3, No. 7, e2841, 30.07.2008.

Research output: Contribution to journalArticle

Öström, M, Loffler, KA, 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, vol. 3, no. 7, e2841. https://doi.org/10.1371/journal.pone.0002841
Öström, Maria ; Loffler, Kelly A. ; Edfalk, Sara ; Selander, Lars ; Dahl, Ulf ; Ricordi, Camillo ; Jeon, Jongmin ; Correa-Medina, Mayrin ; Diez, Juan ; Edlund, Helena. / Retinoic acid promotes the generation of pancreatic endocrine progenitor cells and their further differentiation into β-cells. In: PLoS One. 2008 ; Vol. 3, No. 7.
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