Turning skin into dopamine neurons

Abstract

The possibility to generate neurons from fibroblasts became a reality with the development of iPS technology a few years ago. By reprogramming somatic cells using transcription factor (TF) overexpression, it is possible to generate pluripotent stem cells that then can be differentiated into any somatic cell type including various subtypes of neurons. This raises the possibility of using donor-matched or even patient-specific cells for cell therapy of neuro-logical disorders such as Parkinson's disease (PD), Huntington's disease and stroke. Supporting this idea, dopamine neurons, which are the cells dying in PD, derived from human iPS cells have been demonstrated to survive transplan-tation and reverse motor symptoms in animal models of PD [1]. However, a major problem with the use of pluri-potent cells as starting material for cell replacement therapy is their incomplete differentiation and their propensity to form tumors following transplantation [2]. In a recent issue of Nature, Caiazzo et al. describe an alternative way to reprogram fibroblasts into dopaminer-gic neurons, without going through a pluripotent stage [3]. Caiazzo et al. overexpressed three transcription factors, Mash1, Nurr1 and Lmx1a, in fibroblasts and found efficient and rapid conversion into dopaminergic neurons and show that conversion takes place without going through a pluripotent or even a progenitor cell stage. The induced dopamine neurons displayed several hallmarks of functional dopamine neurons in vitro, including morphology, marker gene expression, electrophysiological and biochemical properties. Importantly, their strategy appeared to be successful in fibroblasts from both mouse and human donors including cells from aged individuals suffering from Parkinson's disease. The study from Caiazzo et al. is a recent addition to a series of publications that demonstrate that direct conversion of fibroblasts into neurons is feasible [3-6]. In a seminal publication by Vier-buchen et al. three transcription factors were also used, in this case Mash1, Brn2, Myt1l, to reprogram mouse fibroblasts into excitatory functional neurons [6]. In a follow up study they then found that the same three factors, with the addition of NeuroD1, were able to generate functional neurons from human fibroblasts [4]. In a recent paper we have used five factors (Mash1, Brn2, Myt1l, Lmx1a, FoxA2) to generate dopamine neurons from human fibroblasts [5]. Thus transcription factor mediated conversion of fibroblasts to neurons appears to be a solid phenomenon that is reproducible among several labs. When looked upon together, these studies firmly establish induced neuronal (iN) cells as a way to generate subtype specific neurons from …

DOI: 10.1038/cr.2011.130

Cite this paper

@article{Parmar2011TurningSI, title={Turning skin into dopamine neurons}, author={Malin Parmar and Johan Jakobsson}, journal={Cell Research}, year={2011}, volume={21}, pages={1386-1387} }