Open AccessDirected Differentiation of Ventral Spinal Progenitors and Motor Neurons from Human Embryonic Stem Cells by Small Molecules
Author(s) -
Li XueJun,
Hu BaoYang,
Jones Stefanie A.,
Zhang YingSha,
LaVaute Timothy,
Du ZhongWei,
Zhang SuChun
Publication year - 2008
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2007-0620
Subject(s) - biology , embryonic stem cell , sonic hedgehog , directed differentiation , induced pluripotent stem cell , microbiology and biotechnology , cellular differentiation , progenitor cell , motor neuron , stem cell , olig2 , neuroscience , spinal cord , genetics , oligodendrocyte , signal transduction , myelin , central nervous system , gene
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.