Directed Differentiation of Ventral Spinal Progenitors and Motor Neurons from Human Embryonic Stem Cells by Small Molecules
Article first published online: 31 JAN 2008
Copyright © 2008 AlphaMed Press
Volume 26, Issue 4, pages 886–893, April 2008
How to Cite
Li, X.-J., Hu, B.-Y., Jones, S. A., Zhang, Y.-S., LaVaute, T., Du, Z.-W. and Zhang, S.-C. (2008), Directed Differentiation of Ventral Spinal Progenitors and Motor Neurons from Human Embryonic Stem Cells by Small Molecules. STEM CELLS, 26: 886–893. doi: 10.1634/stemcells.2007-0620
- Issue published online: 2 JAN 2009
- Article first published online: 31 JAN 2008
- Manuscript Accepted: 22 JAN 2008
- Manuscript Received: 31 JUL 2007
- Stem cell;
- Motor neuron;
- Small molecule;
- Spinal cord
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.