Small-Molecule Inhibitors of Bone Morphogenic Protein and Activin/Nodal Signals Promote Highly Efficient Neural Induction From Human Pluripotent Stem Cells

The balance of bone morphogenic protein (BMP), transforming growth factor-beta (TGF beta)/activin/nodal, and Wnt signals regulates the early lineage segregation of human embryonic stem cells (ESCs). Here we demonstrate that a combination of small-molecule inhibitors of BMP (Dorsomorphin) and TGF beta/activin/nodal (SB431542) signals promotes highly efficient neural induction from both human ESCs and induced pluripotent stem cells (iPSCs). The combination of small molecules had effects on both cell survival and purity of neural differentiation, under conditions of stromal (PA6) cell coculture and feeder-free floating aggregation culture, for all seven pluripotent stem cell lines that we studied, including three ESC and four iPSC lines. Small molecule compounds are stable and cost effective, so our findings provide a promising strategy for controlled production of neurons in regenerative medicine. (C) 2010 Wiley-Liss, Inc.