Stromal Cell–Derived Inducing Activity, Nurr1, and Signaling Molecules Synergistically Induce Dopaminergic Neurons from Mouse Embryonic Stem Cells

To induce differentiation of embryonic stem cells (ESCs) into specialized cell types for therapeutic purposes, it may be desirable to combine genetic manipulation and appropriate differentiation signals. We studied the induction of dopaminergic (DA) neurons from mouse ESCs by overexpressing the transcription factor Nurr1 and coculturing with PA6 stromal cells. Nurr1‐expressing ESCs (N2 and N5) differentiated into a higher number of neurons (∼twofold) than the naïve ESCs (D3). In addition, N2/N5‐derived cells contained a significantly higher proportion (>50%) of tyrosine hydroxylase (TH)+ neurons than D3 (