Format

Send to

Choose Destination
iScience. 2019 Jul 24;19:450-460. doi: 10.1016/j.isci.2019.07.033. [Epub ahead of print]

Connexin 43 Functions as a Positive Regulator of Stem Cell Differentiation into Definitive Endoderm and Pancreatic Progenitors.

Author information

1
Department of Medicine, UW Diabetes Institute, University of Washington, 850 Republican Street, S475, Seattle, WA 98109, USA.
2
Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
3
Institute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, S480, Seattle, WA 98109, USA.
4
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. Electronic address: lcrisa@uw.edu.
5
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. Electronic address: vcirulli@uw.edu.

Abstract

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.

KEYWORDS:

Cell Biology; Specialized Functions of Cells; Stem Cells Research

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center