Neurogenin 2 enhances the generation of patient-specific induced neuronal cells

Neurogenin 2 enhances the generation of patient-specific induced neuronal cells Direct lineage reprogramming of human fibroblasts into functional neurons holds great promise for biomedical applications such as regenerative medicine and cellbased disease modelling. However, clinical applications must consider how to increase neuronal conversion efficiency and at the same time reduce the number of required transcription factors. Here, we investigated whether Neurogenin 2 (Ngn2), which is a proneural gene that directs neuronal differentiation of progenitor cells during development, can enhance the generation of patient-specific induced neuronal cells. In this study, we transfected Ascl1, Sox2 and Ngn2 into human fibroblasts from the patients׳ scalp by lentivirus. Morphological analysis, immunocytochemistry, gene expression and electrophysiological analysis were performed to identify the similarity of induced neuronal cells (iNCs) to human neuronal cells. Ngn2 increase the conversion efficiency from 4% to 13.4%. iNCs express neuronal cell markers and resemble wild-type neurons in their morphology, gene expression profiles and exhibit functional membrane properties of mature neurons. Implanted iNCs can survive and integrate in mouse brains and, unlike iPS cell-derived neural cells, do not generate tumours. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Brain Research Elsevier

Neurogenin 2 enhances the generation of patient-specific induced neuronal cells

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Publisher
Elsevier
Copyright
Copyright © 2015 Elsevier B.V.
ISSN
0006-8993
D.O.I.
10.1016/j.brainres.2015.04.027
Publisher site
See Article on Publisher Site

Abstract

Direct lineage reprogramming of human fibroblasts into functional neurons holds great promise for biomedical applications such as regenerative medicine and cellbased disease modelling. However, clinical applications must consider how to increase neuronal conversion efficiency and at the same time reduce the number of required transcription factors. Here, we investigated whether Neurogenin 2 (Ngn2), which is a proneural gene that directs neuronal differentiation of progenitor cells during development, can enhance the generation of patient-specific induced neuronal cells. In this study, we transfected Ascl1, Sox2 and Ngn2 into human fibroblasts from the patients׳ scalp by lentivirus. Morphological analysis, immunocytochemistry, gene expression and electrophysiological analysis were performed to identify the similarity of induced neuronal cells (iNCs) to human neuronal cells. Ngn2 increase the conversion efficiency from 4% to 13.4%. iNCs express neuronal cell markers and resemble wild-type neurons in their morphology, gene expression profiles and exhibit functional membrane properties of mature neurons. Implanted iNCs can survive and integrate in mouse brains and, unlike iPS cell-derived neural cells, do not generate tumours.

Journal

Brain ResearchElsevier

Published: Jul 30, 2015

References

  • Direct generation of functional dopaminergic neurons from mouse and human fibroblasts
    Caiazzo, M.; Dell’Anno, M.T.; Dvoretskova, E.; Lazarevic, D.; Taverna, S.; Leo, D.; Sotnikova, T.D.; Menegon, A.; Roncaglia, P.; Colciago, G.; Russo, G.; Carninci, P.; Pezzoli, G.; Gainetdinov, R.R.; Gustincich, S.; Dityatev, A.; Broccoli, V.
  • Roles of bHLH genes in neural stem cell differentiation
    Kageyama, R.; Ohtsuka, T.; Hatakeyama, J.; Ohsawa, R.
  • Induction of human neuronal cells by defined transcription factors
    Pang, Z.P.; Yang, N.; Vierbuchen, T.; Ostermeier, A.; Fuentes, D.R.; Yang, T.Q.; Citri, A.; Sebastiano, V.; Marro, S.; Sudhof, T.C.; Wernig, M.
  • Direct conversion of fibroblasts to functional neurons by defined factors
    Vierbuchen, T.; Ostermeier, A.; Pang, Z.P.; Kokubu, Y.; Sudhof, T.C.; Wernig, M.
  • Direct conversion of fibroblasts to functional neurons
    Yashar, M.; Kalani, S.; Martirosyan, N.

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