Recent reports have demonstrated that somatic cells can be directly converted to other differentiated cell types through ectopic expression of sets of transcription factors, directly avoiding the transition through a pluripotent state. Our previous experiments generated induced neural progenitor-like cells (iNPCs) by a novel combination of five transcription factors (Sox2, Brn2, TLX, Bmi1 and c-Myc). Here we demonstrated that the iNPCs not only possess NPC-specific marker genes, but also have qualities of primary brain-derived NPCs (WT-NPCs), including tripotent differentiation potential, mature neuron differentiation capability and synapse formation. Importantly, the mature neurons derived from iNPCs exhibit significant physiological properties, such as potassium channel activity and generation of action potential-like spikes. These results suggest that directly reprogrammed iNPCs closely resemble WT-NPCs, which may suggest an alternative strategy to overcome the restricted proliferative and lineage potential of induced neurons (iNCs) and broaden applications of cell therapy in the treatment of neurodegenerative disorders.
|State||Published - 2013|
Bibliographical noteFunding Information:
We kindly thank Drs. Yulong Li, Jinxu Liu and Lie Gao, and Mrs. Kristin M. Leland Wavrin, who provided technical support for this work. Julie Ditter, Lenal Bottoms, Johna Belling, and Robin Taylor provided outstanding administrative and secretarial support. Monoclonal antibody against PAX6 was obtained from the Developmental Studies Hybridoma Bank maintained by the University of Iowa, Department of Biological Sciences, Iowa City, IA 52242. This work was supported in part by research grants by the National Institutes of Health: R01 NS 41858-01, R01 NS 061642-01, 3R01NS61642-2S1, P01 NS043985, and P20 RR15635-01 (JZ), the State of Nebraska, DHHS-LB606 Stem Cell 2009-10 (JZ), LB606 Stem Cell-2010-10 (SD and CT), National Natural Science Foundation of China (NSFC) # 81028007 (JZ) and National Natural Science Foundation of China (NSFC) #81271419 (CT).
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