Inhibitors of Src and focal adhesion kinase promote endocrine specification: impact on the derivation of β-cells from human pluripotent stem cells.

ABSTRACT: Stepwise approaches for the derivation of β-cells from human embryonic stem cells have been described. However, low levels of endocrine specification limit the final yield of insulin-producing β-cells. In this study, we show that the pyrrolo-pyrimidine Src family kinase (SFK) inhibitor PP2 effectively promotes the endocrine specification of human embryonic stem cell derivatives based on its capacity to induce the expression of proendocrine transcription factors (NGN3, NEUROD1, NKX2.2, and PAX4) and to significantly increase the final yield of insulin-positive cells. We further demonstrate that PP2 inhibits the activation of focal adhesion kinase (FAK), and selective inhibition of this kinase is also sufficient to induce early endocrine commitment based on increased expression of NGN3, NEUR

SUBMITTER: Afrikanova I 

PROVIDER: S-EPMC3195622 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature