Work

Synthetic small molecules that control stem cell fate

Year: 2003

Type: article

Abstract: In an attempt to better understand and control the processes that regulate stem cell fate, we have set out to identify small molecules that induce neuronal differentiation in embryonic stem cells (ESCs). A high-throughput phenotypic cell-based screen of kinase-directed combinatorial libraries led to the discovery of TWS119, a 4,6-disubstituted pyrrolopyrimidine that can induce neurogenesis in murine ESCs. The target of TWS119 was shown to be glycogen synthase kinase-3beta (GSK-3beta) by both affinity-based and biochemical methods. This study provides evidence that GSK-3beta is involved in the induction of mammalian neurogenesis in ESCs. This and such other molecules are likely to provide insights into the molecular mechanisms that control stem cell fate, and may ultimately be useful to in vivo stem cell biology and therapy.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.0732087100

Authors: Sheng Ding, Tom Y. H. Wu, Achim Brinker, Eric C. Peters, Wooyoung Hur, Nathanael S. Gray, Peter G. Schultz

Institutions: Scripps Research Institute, Genomics Institute of the Novartis Research Foundation

Language: English

Topic: Pluripotent Stem Cells Research

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

OpenAlex ID: W1972747946

FWCI: 7.072

Cites: 26

Cited by: 379

Related to: 10