Connexin 43 Functions as a Positive Regulator of Stem Cell Differentiation into Definitive Endoderm and Pancreatic Progenitors
Wendy Yang,
Paul D. Lampe,
Patricia Kensel-Hammes,
Jennifer Hesson,
Carol B. Ware,
Laura Crisa,
Vincenzo Cirulli
Affiliations
Wendy Yang
Department of Medicine, UW Diabetes Institute, University of Washington, 850 Republican Street, S475, Seattle, WA 98109, USA
Paul D. Lampe
Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Patricia Kensel-Hammes
Department of Medicine, UW Diabetes Institute, University of Washington, 850 Republican Street, S475, Seattle, WA 98109, USA
Jennifer Hesson
Institute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, S480, Seattle, WA 98109, USA
Carol B. Ware
Institute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, S480, Seattle, WA 98109, USA
Laura Crisa
Department of Medicine, UW Diabetes Institute, University of Washington, 850 Republican Street, S475, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, S480, Seattle, WA 98109, USA; Department of Pharmacology, University of Washington, Seattle, WA, USA; Corresponding author
Vincenzo Cirulli
Department of Medicine, UW Diabetes Institute, University of Washington, 850 Republican Street, S475, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, S480, Seattle, WA 98109, USA; Department of Pharmacology, University of Washington, Seattle, WA, USA; Corresponding author
Summary: Efficient stem cell differentiation into pancreatic islet cells is of critical importance for the development of cell replacement therapies for diabetes. Here, we identify the expression pattern of connexin 43 (Cx43), a gap junction (GJ) channel protein, in human embryonic stem cell (hESC)-derived definitive endoderm (DE) and primitive gut tube cells, representing early lineages for posterior foregut (PF), pancreatic progenitors (PP), pancreatic endocrine progenitors (PE), and islet cells. As the function of GJ channels is dependent on their gating status, we tested the impact of supplementing hESC-derived PP cell cultures with AAP10, a peptide that promotes Cx43 GJ channel opening. We found that this treatment promotes the expression of DE markers FoxA2 and Sox17, leads to a more efficient derivation of DE, and improves the yield of PF, PP, and PE cells. These results demonstrate a functional involvement of GJ channels in the differentiation of embryonic stem cells into pancreatic cell lineages. : Cell Biology; Stem Cells Research; Specialized Functions of Cells Subject Areas: Cell Biology, Stem Cells Research, Specialized Functions of Cells
