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- 2017.1
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Developmental information aids stem cell biologists in producing tissue-specific cells. Recapitulation of the developmental profile of a specific cell type in an in vitro stem cell system provides a strategy for manipulating cell-fate choice during the differentiation process. Nurr1 and Foxa2 are potential candidates for genetic engineering to generate midbrain-type dopamine (DA) neurons for experimental and therapeutic applications in Parkinson’s disease (PD), as forced expression of these genes in neural stem/precursor cells (NPCs) yields cells with a complete battery of midbrain DA neuron-specific genes. However, simple overexpression without considering their expression pattern in the developing midbrain tends to generate DA cells without adequate neuronal maturation and long-term maintenance of their phenotype in vitro and in vivo after transplantation. We here show that the physiological levels and timing of Nurr1 and Foxa2 expression can be replicated in NPCs by choosing the right vectors and promoters. Controlled expression combined with a strategy for transgene expression maintenance induced generation of fully mature midbrain-type DA neurons. These findings demonstrate the feasibility of cellular engineering for artificial cell-fate specification.
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참고문헌 (23)
참고문헌 신청
Ang SL / 2009 / Foxa1 and Foxa2 transcription factors regulate differentiation of midbrain dopaminergic neurons / Adv Exp Med Biol 651 : 58 ~ 65
Barzilai A / 2003 / Molecular mechanisms of selective dopaminergic neuronal death in Parkinson’s disease / Trends Mol Med 9 : 126 ~ 132
Castillo SO / 1998 / Dopamine biosynthesis is selectively abolished in substantia nigra/ventral tegmental area but not in hypothalamic neurons in mice with targeted disrupti
Deierborg T / 2008 / Emerging restorative treatments for Parkinson's disease / Prog Neurobiol 85 : 407 ~ 432
Ferri AL / 2007 / Foxa1 and Foxa2 regulate multiple phases of midbrain dopaminergic neuron development in a dosage-dependent manner / Development 134 : 2761 ~ 2769
Barzilai A / 2003 / Molecular mechanisms of selective dopaminergic neuronal death in Parkinson’s disease / Trends Mol Med 9 : 126 ~ 132
Castillo SO / 1998 / Dopamine biosynthesis is selectively abolished in substantia nigra/ventral tegmental area but not in hypothalamic neurons in mice with targeted disrupti
Deierborg T / 2008 / Emerging restorative treatments for Parkinson's disease / Prog Neurobiol 85 : 407 ~ 432
Ferri AL / 2007 / Foxa1 and Foxa2 regulate multiple phases of midbrain dopaminergic neuron development in a dosage-dependent manner / Development 134 : 2761 ~ 2769
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