Characterization of induced neural progenitors from skin fibroblasts by a novel combination of defined factors

Changhai Tian; Qiang Liu; Kangmu Ma; Yongxiang Wang; Qiang Chen; Randall Ambroz; David L. Klinkebiel; Yuju Li; Yunlong Huang; Jianqing Ding; Jie Wu; Jialin C. Zheng

doi:10.1038/srep01345

Characterization of induced neural progenitors from skin fibroblasts by a novel combination of defined factors

Changhai Tian, Qiang Liu, Kangmu Ma, Yongxiang Wang, Qiang Chen, Randall Ambroz, David L. Klinkebiel, Yuju Li, Yunlong Huang, Jianqing Ding, Jie Wu, Jialin C. Zheng

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Abstract

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.

Original language	English
Article number	1345
Journal	Scientific Reports
Volume	3
DOIs	https://doi.org/10.1038/srep01345
State	Published - 2013

Bibliographical note

Funding 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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title = "Characterization of induced neural progenitors from skin fibroblasts by a novel combination of defined factors",

abstract = "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.",

author = "Changhai Tian and Qiang Liu and Kangmu Ma and Yongxiang Wang and Qiang Chen and Randall Ambroz and Klinkebiel, {David L.} and Yuju Li and Yunlong Huang and Jianqing Ding and Jie Wu and Zheng, {Jialin C.}",

note = "Funding 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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AU - Tian, Changhai

AU - Liu, Qiang

AU - Ma, Kangmu

AU - Wang, Yongxiang

AU - Chen, Qiang

AU - Ambroz, Randall

AU - Klinkebiel, David L.

AU - Li, Yuju

AU - Huang, Yunlong

AU - Ding, Jianqing

AU - Wu, Jie

AU - Zheng, Jialin C.

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PY - 2013

Y1 - 2013

N2 - 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.

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Characterization of induced neural progenitors from skin fibroblasts by a novel combination of defined factors

Abstract

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