Proneural Transcription Factor Atoh1 Drives Highly Efficient Differentiation of Human Pluripotent Stem Cells Into Dopaminergic Neurons
作者： Jonathan Sagal , Xiping Zhan , Jinchong Xu , Jessica Tilghman , Senthilkumar S. Karuppagounder
关键词:
摘要: Human pluripotent stem cells (PSCs) are a promising cell resource for various applications in regenerative medicine. Highly efficient approaches that differentiate human PSCs into functional lineage-specific neurons critical modeling neurological disorders and testing potential therapies. Proneural transcription factors crucial drivers of neuron development hold promise driving highly neuronal conversion PSCs. Here, we study the functions proneural factor Atoh1 differentiation We show is induced during ectopic expression sufficient to drive with high efficiency. induction, combination extrinsic factors, differentiates dopaminergic (DA) >80% purity. Atoh1-induced DA recapitulate key biochemical electrophysiological features midbrain neurons, degeneration which responsible clinical symptoms Parkinson's disease (PD). provide reliable model studying PD pathogenesis, such as neurotoxin-induced neurodegeneration PD. Overall, our results determine role regulating subtype specification Our Atoh1-mediated approach will enable large-scale patient-derived mechanistic studies drug screening both familial sporadic
elsevier.com
alphamedpress.org参考文章(44)
AA Grace, BS Bunney, The control of firing pattern in nigral dopamine neurons: single spike firing The Journal of Neuroscience. ,vol. 4, pp. 2866- 2876 ,(1984) , 10.1523/JNEUROSCI.04-11-02866.1984
Huda Y. Zoghbi, Andrew L. Abney, Amy W. Helms, Jane E. Johnson, Nissim Ben-Arie, Autoregulation and multiple enhancers control Math1 expression in the developing nervous system. Development. ,vol. 127, pp. 1185- 1196 ,(2000) , 10.1242/DEV.127.6.1185
Maria Sundberg, Helle Bogetofte, Tristan Lawson, Johan Jansson, Gaynor Smith, Arnar Astradsson, Michele Moore, Teresia Osborn, Oliver Cooper, Roger Spealman, Penelope Hallett, Ole Isacson, Improved Cell Therapy Protocols for Parkinson's Disease Based on Differentiation Efficiency and Safety of hESC-, hiPSC-, and Non-Human Primate iPSC-Derived Dopaminergic Neurons† Stem Cells. ,vol. 31, pp. 1548- 1562 ,(2013) , 10.1002/STEM.1415
AA Grace, BS Bunney, The control of firing pattern in nigral dopamine neurons: burst firing The Journal of Neuroscience. ,vol. 4, pp. 2877- 2890 ,(1984) , 10.1523/JNEUROSCI.04-11-02877.1984
A. Grace, B. Bunney, Nigral Dopamine Neurons: Intracellular Recording and Identification with L-Dopa Injection and Histofluorescence Science. ,vol. 210, pp. 654- 656 ,(1980) , 10.1126/SCIENCE.7433992
Hiroshi Kawasaki, Kenji Mizuseki, Satomi Nishikawa, Satoshi Kaneko, Yoshihisa Kuwana, Shigetada Nakanishi, Shin-Ichi Nishikawa, Yoshiki Sasai, Induction of midbrain dopaminergic neurons from ES cells by stromal cell-derived inducing activity. Neuron. ,vol. 28, pp. 31- 40 ,(2000) , 10.1016/S0896-6273(00)00083-0
Yong Wook Jung, Eriona Hysolli, Kun-Yong Kim, Yoshiaki Tanaka, In-Hyun Park, Human induced pluripotent stem cells and neurodegenerative disease: prospects for novel therapies Current Opinion in Neurology. ,vol. 25, pp. 125- 130 ,(2012) , 10.1097/WCO.0B013E3283518226
Liang Qiang, Ryousuke Fujita, Asa Abeliovich, None, Remodeling neurodegeneration: somatic cell reprogramming-based models of adult neurological disorders. Neuron. ,vol. 78, pp. 957- 969 ,(2013) , 10.1016/J.NEURON.2013.06.002
T. J. Klisch, Y. Xi, A. Flora, L. Wang, W. Li, H. Y. Zoghbi, In vivo Atoh1 targetome reveals how a proneural transcription factor regulates cerebellar development Proceedings of the National Academy of Sciences of the United States of America. ,vol. 108, pp. 3288- 3293 ,(2011) , 10.1073/PNAS.1100230108
Nissim Ben-Arie, Hugo J. Bellen, Dawna L. Armstrong, Alanna E. McCall, Polina R. Gordadze, Qiuxia Guo, Martin M. Matzuk, Huda Y. Zoghbi, Math1 is essential for genesis of cerebellar granule neurons. Nature. ,vol. 390, pp. 169- 172 ,(1997) , 10.1038/36579