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EMBRYONIC STEM CELLS

Directed Differentiation of Ventral Spinal Progenitors and Motor Neurons from Human Embryonic Stem Cells by Small Molecules

Departments of Anatomy and Neurology and the Stem Cell Research Program, Waisman Center, University of Wisconsin, Madison, Wisconsin, USA

Key Words. Stem cell • Motor neuron • Small molecule • Spinal cord

Correspondence: Su-Chun Zhang, M.D., Ph.D., Waisman Center, Room T613, University of Wisconsin, 1500 Highland Avenue, Madison, Wisconsin 53705, USA. Telephone: 608-265-2543; Fax: 608-263-5267; e-mail: zhang{at}waisman.wisc.edu

Received July 31, 2007; accepted for publication January 22, 2008.
First published online in STEM CELLS EXPRESS   January 31, 2008.



Specification of distinct cell types from human embryonic stem cells (hESCs) is key to the potential application of these naïve pluripotent cells in regenerative medicine. Determination of the nontarget differentiated populations, which is lacking in the field, is also crucial. Here, we show an efficient differentiation of motor neurons (50%) by a simple sequential application of retinoid acid and sonic hedgehog (SHH) in a chemically defined suspension culture. We also discovered that purmorphamine, a small molecule that activates the SHH pathway, could replace SHH for the generation of motor neurons. Immunocytochemical characterization indicated that cells differentiated from hESCs were nearly completely restricted to the ventral spinal progenitor fate (NKX2.2+, Irx3+, and Pax7–), with the exception of motor neurons (HB9+) and their progenitors (Olig2+). Thus, the directed neural differentiation system with small molecules, even without further purification, will facilitate basic and translational studies using human motoneurons at a minimal cost.

Disclosure of potential conflicts of interest is found at the end of this article.