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Biological Chemistry

Route To Pancreatic Cells

Small molecule directs differentiation

by Sarah Everts
March 17, 2009

A newly discovered small molecule could help differentiate human embryonic stem cells into pancreatic progenitor cells. Pancreatic progenitor cells generate all cells in the pancreas, including the beta cells destroyed in type 1 diabetes. The small molecule, called (–)-indolactam V, could help enable the in vitro growth of pancreatic β cells for use by diabetics and could also be a tool for understanding how embryonic stem cell differentiation occurs.

A team of Harvard University researchers led by chemist Stuart L. Schreiber and developmental biologists Lee L. Rubin and Douglas Melton found the molecule during a screen of a 5,000-compound chemical library (Nat. Chem. Biol., DOI: 10.1038/nchembio.154).

Although researchers can achieve the differentiation of embryonic cells into pancreatic progenitor cells by using cocktails of endogenous molecules, including components such as retinoic acid, the team was motivated by the idea that small-molecule inducers could be "less expensive, more easily controlled, and possibly more efficient than growth factors in directing differentiation," the authors note.

The work is "significant," comments Sheng Ding, a chemist at Scripps Research Institute. Ding points out that there is "a real opportunity to use the new molecule to understand the mechanism behind pancreatic β [cell] differentiation."

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