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A small molecule that directs differentiation of human ESCs into the pancreatic lineage.

Publication TypeJournal Article
AuthorsChen, S., Borowiak M., Fox JL, Maehr R., Osafune K., Davidow L., Lam K., Peng LF, Schreiber SL, Rubin LL, and Melton D.
AbstractStepwise differentiation from embryonic stem cells (ESCs) to functional insulin-secreting beta cells will identify key steps in beta-cell development and may yet prove useful for transplantation therapy for diabetics. An essential step in this schema is the generation of pancreatic progenitors--cells that express Pdx1 and produce all the cell types of the pancreas. High-content chemical screening identified a small molecule, (-)-indolactam V, that induces differentiation of a substantial number of Pdx1-expressing cells from human ESCs. The Pdx1-expressing cells express other pancreatic markers and contribute to endocrine, exocrine and duct cells, in vitro and in vivo. Further analyses showed that (-)-indolactam V works specifically at one stage of pancreatic development, inducing pancreatic progenitors from definitive endoderm. This study describes a chemical screening platform to investigate human ESC differentiation and demonstrates the generation of a cell population that is a key milepost on the path to making beta cells.
Year of Publication2009
JournalNature chemical biology
Volume5
Issue4
Pages258-65
Date Published (YYYY/MM/DD)2009/04/01
ISSN Number1552-4450
DOI10.1038/nchembio.154
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/19287398?dopt=Abstract