Chemicals that modulate stem cell differentiation

doi:10.1073/pnas.0802825105

Chemicals that modulate stem cell differentiation

*Cardiovascular Research Institute,
^‡Department of Physiology, and
^§Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea;
^¶Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea;
^‖CHA Stem Cell Institute, Pochon CHA University College of Medicine, Seoul 135-081, Korea;
**Department of Pediatrics, Washington University School of Medicine, 606 South Euclid Avenue, St. Louis, MO 63108;
^††Department of Chemistry, University of California, Berkeley, CA 94720; and
^‡‡Stem Cell Research Center, Seoul 120-752, Korea

Contributed by Sung-Hou Kim, March 24, 2008 (received for review November 15, 2007)

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.

Footnotes

^†To whom correspondence may be addressed. E-mail: kchwang{at}yuhs.ac, shkim{at}cchem.berkeley.edu, or dwkim2{at}yuhs.ac
Author contributions: K.-C.H., S.-H.K., and D.-W.K. designed research; J.Y.K., W.C., D.-S.K., S.L., S.-M.K., B.-W.S., H.-Y.H., Y.J.H., D.-Y.H., H.S., Y.J., and N.C. performed research; K.-C.H., S.-H.K., and D.-W.K. contributed new reagents/analytic tools; K.-C.H., J.Y.K., W.C., D.-S.K., S.L., S.-M.K., B.-W.S., H.-Y.H., Y.J.H., I.-G.C., D.-Y.H., H.S., Y.J., N.C., S.-H.K., and D.-W.K. analyzed data; and K.-C.H., S.-H.K., and D.-W.K. wrote the paper.
The authors declare no conflict of interest.