Nurr1 and Lmx1a. The efficiency of induction of TH-positive cells was reported to be 18% relying on a TH-EGFP transgenic reporter line. The TH-positive cells co-expressed vesicular monoamine transporter 2 (VMAT2), dopamine transporter (DAT), aldehyde dehydrogenase 1a1 (ALDH1A1), and calbindin. In contrast to the BAM/Foxa2/Lmx1a cells described by Pfisterer et al., the Ascl1/Nurr1/Lmx1a iN cells were able to release dopamine as determined by amperometry and HPLC analysis, indicating that the cells possessed an important functional property of dopamine neurons. Intriguingly, similar results could be obtained using human fibroblasts and the same reprogramming factors. However, the cells generated in this study did not express any regional markers specific to midbrain and displayed immature morphologies. Moreover, the authors did not investigate whether the cells were competent to receive synaptic input. Therefore, despite the use of midbrain dopamine neuron-specific transcription factors for reprogramming, only generic dopamine neuron and no midbrain-specific features were observed, suggesting incomplete reprogramming. Similarly, genome-wide transcriptional profiling showed substantial differences between the reprogrammed and brain-derived dopamine neurons.
