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Neural cells play an inhibitory role in pancreatic differentiation of pluripotent stem cells.

ABSTRACT: Pancreatic endocrine ?-cells derived from embryonic stem (ES) cells and induced pluripotent stem (iPS) cells have received attention as screening systems for therapeutic drugs and as the basis for cell-based therapies. Here, we used a 12-day ?-cell differentiation protocol for mouse ES cells and obtained several hit compounds that promoted ?-cell differentiation. One of these compounds, mycophenolic acid (MPA), effectively promoted ES cell differentiation with a concomitant reduction of neuronal cells. The existence of neural cell-derived inhibitory humoral factors for ?-cell differentiation was suggested using a co-culture system. Based on gene array analysis, we focused on the Wnt/?-catenin pathway and showed that the Wnt pathway inhibitor reversed MPA-induced ?-cell differentiation. Wnt pathway activation promoted ?-cell differentiation also in human iPS cells. Our results showed that Wnt signaling activation positively regulates ?-cell differentiation, and represent a downstream target of the neural inhibitory factor.

SUBMITTER: Nakashima R 

PROVIDER: S-EPMC4738370 | BioStudies | 2015-01-01

REPOSITORIES: biostudies

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