Development

Endoderm Induction

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Science  24 Apr 2009:
Vol. 324, Issue 5926, pp. 440-441
DOI: 10.1126/science.324_440d

There is great interest in generating pluripotent stem cells that might be used in regenerative therapies. However, before such cells can be applied effectively, methods that enable the directed differentiation of stem cells into a desired cell type, such as endoderm cells for the treatment of type I diabetes, are needed. The biological signaling factors activin A and Nodal are known inducers of endoderm, but Borowiak et al. have set out to find small, cellpermeant molecules that could channel embryonic stem cells into an endodermal lineage. Starting with a collection of 4000 compounds, they identified 27 primary hits—chemicals that promoted the expression of an endodermal marker—and further narrowed this list by negative selection and the examination of cell morphology to 2. These heptanoic acid derivatives (IDE1 and IDE2) directed the differentiation of roughly 70 to 80% of mouse and human embryonic stem cells into definitive endoderm. IDE1 and IDE2 come from a library of histone deacetylase inhibitors and appear to act through activation of the TGF-β signaling pathway.

Cell Stem Cell 4, 348 (2009).

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