Chemicals that modulate stem cell differentiation.
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.
Hwang
Ki-Chul
KC
Cardiovascular Research Institute, Department of Physiology, and Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
Kim
Ji Young
JY
Chang
Woochul
W
Kim
Dae-Sung
DS
Lim
Soyeon
S
Kang
Sang-Moon
SM
Song
Byeong-Wook
BW
Ha
Hye-Yeong
HY
Huh
Yong Joon
YJ
Choi
In-Geol
IG
Hwang
Dong-Youn
DY
Song
Heesang
H
Jang
Yangsoo
Y
Chung
Namsik
N
Kim
Sung-Hou
SH
Kim
Dong-Wook
DW
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
D047428:Protein Kinase Inhibitors