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

• Published in: iScience Vol. 19; pp. 450 - 460
• Main Authors: Yang, Wendy, Lampe, Paul D., Kensel-Hammes, Patricia, Hesson, Jennifer, Ware, Carol B., Crisa, Laura, Cirulli, Vincenzo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 27.09.2019; Elsevier
• Subjects: Cell Biology; Specialized Functions of Cells; Stem Cells Research; Stem Cells Research; Specialized Functions of Cells; Cell Biology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2019.07.033

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. [Display omitted] •Cx43 is upregulated during hESC differentiation into definitive endoderm (DE)•siRNA-mediated knockdown of Cx43 prevents hESC differentiation into DE cells•AAP10-mediated gating of Cx43 gap junctions promotes the expression of FoxA2 and Sox17•Cx43 gap junction communication supports DE and pancreatic progenitors development Cell Biology; Stem Cells Research; Specialized Functions of Cells