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PMID: 19287398 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Nature chemical biology ·Vol. 5 ·No. 4 ·2009-04-00 ·Pages 258-65

Chen S, Borowiak M, Fox JL, Maehr R, Osafune K, Davidow L, Lam K, Peng LF, Schreiber SL, Rubin LL, Melton D

Abstract

Stepwise 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.

MeSH Terms
Animals Biomarkers Carcinogens/pharmacology Cell Differentiation/drug effects Cell Line Embryonic Stem Cells/cytology,drug effects,physiology Homeodomain Proteins/metabolism Humans Indoles/pharmacology Insulin-Secreting Cells/cytology Lactams/pharmacology Mice Trans-Activators/metabolism
Chemicals
Biomarkers Carcinogens Homeodomain Proteins Indoles Lactams Trans-Activators pancreatic and duodenal homeobox 1 protein indolactam V
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Chen Shuibing
Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Cambridge, Massachusetts, USA.
Borowiak Malgorzata
Fox Julia L
Maehr René
Osafune Kenji
Davidow Lance
Lam Kelvin
Peng Lee F
Schreiber Stuart L
Rubin Lee L
Melton Douglas
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Article Info
Journal
Nature chemical biology
Abbr.
Nat Chem Biol
ISSN
1552-4469
DOI
10.1038/nchembio.154
Published
2009-04-00
Epub
2009-00-15
Pages
258-65
Language
English
Region
United States
NLM ID
101231976
Subset
IM
Grants
Howard Hughes Medical Institute · United States
Databases
PubChem-Substance
57244616, 57244617, 57244618, 57244619, 57244620, 57244621, 57244622, 57244623, 57244624, 57244625, 57244626, 57244627, 57244628, 57244629, 57244630, 57244631, 57244632, 57244633, 57244634
Corrections
CommentIn
PMID: 19295520
External Links
PubMed source DOI: 10.1038/nchembio.154 View journal details
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