title: Self-renewal of embryonic stem cells by a small molecule.
abstract: A cell-based screen of chemical libraries was carried out to identify small molecules that control the self-renewal of ES cells. A previously uncharacterized heterocycle, SC1, was discovered that allows one to propagate murine ES cells in an undifferentiated, pluripotent state under chemically defined conditions in the absence of feeder cells, serum, and leukemia inhibitory factor. Long-term SC1-expanded murine ES cells can be differentiated into cells of the three primary germ layers in vitro and also can generate chimeric mice and contribute to the germ line in vivo. Biochemical and cellular experiments suggest that SC1 works through dual inhibition of RasGAP and ERK1. Molecules of this kind may not only facilitate practical applications of stem cells in research and therapy, but also provide previously undescribed insights into the complex biology of stem cells.
authors.affiliation: Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Shuibing
authors.initials: S
authors.lastname: Chen
authors.forename: Jeong Tae
authors.initials: JT
authors.lastname: Do
authors.forename: Qisheng
authors.initials: Q
authors.lastname: Zhang
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Yao
authors.forename: Feng
authors.initials: F
authors.lastname: Yan
authors.forename: Eric C
authors.initials: EC
authors.lastname: Peters
authors.forename: Hans R
authors.initials: HR
authors.lastname: Schöler
authors.forename: Peter G
authors.initials: PG
authors.lastname: Schultz
authors.forename: Sheng
authors.initials: S
authors.lastname: Ding
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: D011720:Pyrazoles; D011743:Pyrimidines; C515825:SC1 compound