In vitro differentiation of stem cells has the potential to generate specific cell types for clinical use but, to date, this approach has mainly created cells with unsatisfactory phenotypes. Now, Sang-Hun Lee and colleagues generate mature dopamine (DA) neurons from rat neural progenitor cells (NPCs; see p. 2447). Midbrain DA neurons, which are the main source of dopamine in the mammalian nervous system, are lost in Parkinson’s disease. Previous attempts to induce NPC differentiation into DA neurons through the forced expression of Nurr1, a transcription factor that is expressed during midbrain development, induced DA-specific marker expression but failed to generate mature DA neurons. Here, by using an inducible retroviral vector system to express less exogenous Nurr1, and at a later time point than used previously, the researchers generate morphologically and phenotypically mature DA neurons from NPCs. Adjustment of the levels and timings of the expression of cell type-specific transcription factors to match physiological conditions, suggest the researchers, could facilitate the in vitro generation of other useful cell types.
Making dopamine neurons: less Nurr1 later is more
Making dopamine neurons: less Nurr1 later is more. Development 1 July 2012; 139 (13): e1305. doi:
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