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Publication : Conversion of Astrocytes and Fibroblasts into Functional Noradrenergic Neurons.

First Author  Li S Year  2019
Journal  Cell Rep Volume  28
Issue  3 Pages  682-697.e7
PubMed ID  31315047 Mgi Jnum  J:298893
Mgi Id  MGI:6488846 Doi  10.1016/j.celrep.2019.06.042
Citation  Li S, et al. (2019) Conversion of Astrocytes and Fibroblasts into Functional Noradrenergic Neurons. Cell Rep 28(3):682-697.e7
abstractText  Dysfunction of noradrenergic (NA) neurons is associated with a number of neuronal disorders. Diverse neuronal subtypes can be generated by direct reprogramming. However, it is still unknown how to convert non-neuronal cells into NA neurons. Here, we show that seven transcription factors (TFs) (Ascl1, Phox2b, AP-2alpha, Gata3, Hand2, Nurr1, and Phox2a) are able to convert astrocytes and fibroblasts into induced NA (iNA) neurons. These iNA neurons express the genes required for the biosynthesis, release, and re-uptake of noradrenaline. Moreover, iNA neurons fire action potentials, receive synaptic inputs, and control the beating rate of co-cultured ventricular myocytes. Furthermore, iNA neurons survive and integrate into neural circuits after transplantation. Last, human fibroblasts can be converted into functional iNA neurons as well. Together, iNA neurons are generated by direct reprogramming, and they could be potentially useful for disease modeling and cell-based therapies.
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