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Biological Chemistry

Indolactam Directs Stem Cell Differentiation

Small molecule paves route to pancreatic cells

by Sarah Everts
March 23, 2009 | A version of this story appeared in Volume 87, Issue 12

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 also could 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 for compounds that inspire embryonic stem cells to become pancreatic progenitor cells (Nat. Chem. Biol., DOI: 10.1038/nchembio.154). Although researchers can trigger differentiation of embryonic cells into pancreatic progenitor cells 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. Sheng Ding, a chemist at Scripps Research Institute, 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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