title: Chemicals that modulate stem cell differentiation.
abstract: Important cellular processes such as cell fate are likely to be controlled by an elaborate orchestration of multiple signaling pathways, many of which are still not well understood or known. Because protein kinases, the members of a large family of proteins involved in modulating many known signaling pathways, are likely to play important roles in balancing multiple signals to modulate cell fate, we focused our initial search for chemical reagents that regulate stem cell fate among known inhibitors of protein kinases. We have screened 41 characterized inhibitors of six major protein kinase subfamilies to alter the orchestration of multiple signaling pathways involved in differentiation of stem cells. We found that some of them cause recognizable changes in the differentiation rates of two types of stem cells, rat mesenchymal stem cells (MSCs) and mouse embryonic stem cells (ESCs). Among many, we describe the two most effective derivatives of the same scaffold compound, isoquinolinesulfonamide, on the stem cell differentiation: rat MSCs to chondrocytes and mouse ESCs to dopaminergic neurons.
authors.affiliation: Cardiovascular Research Institute, Department of Physiology, and Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Ki-Chul
authors.initials: KC
authors.lastname: Hwang
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Woochul
authors.initials: W
authors.lastname: Chang
authors.forename: Dae-Sung
authors.initials: DS
authors.lastname: Kim
authors.forename: Soyeon
authors.initials: S
authors.lastname: Lim
authors.forename: Sang-Moon
authors.initials: SM
authors.lastname: Kang
authors.forename: Byeong-Wook
authors.initials: BW
authors.lastname: Song
authors.forename: Hye-Yeong
authors.initials: HY
authors.lastname: Ha
authors.forename: Yong Joon
authors.initials: YJ
authors.lastname: Huh
authors.forename: In-Geol
authors.initials: IG
authors.lastname: Choi
authors.forename: Dong-Youn
authors.initials: DY
authors.lastname: Hwang
authors.forename: Heesang
authors.initials: H
authors.lastname: Song
authors.forename: Yangsoo
authors.initials: Y
authors.lastname: Jang
authors.forename: Namsik
authors.initials: N
authors.lastname: Chung
authors.forename: Sung-Hou
authors.initials: SH
authors.lastname: Kim
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Kim
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D019902:Chondrocytes / Q000166:cytology; D053595:Embryonic Stem Cells / Q000187:drug effects* / Q000201:enzymology; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D009474:Neurons / Q000166:cytology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051381:Rats
chemical_list: D047428:Protein Kinase Inhibitors