Transcription factor-induced lineage programming of noradrenaline and motor neurons from embryonic stem cells
An important goal in stem cell biology is to develop methods for efficient generation of clinically interesting cell types from relevant stem cell populations. This is particularly challenging for different types of neurons of the central nervous system where hundreds of distinct neuronal cell types...
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sg-ntu-dr.10356-1028212020-03-07T12:24:54Z Transcription factor-induced lineage programming of noradrenaline and motor neurons from embryonic stem cells Mong, Jamie Panman, Lia Alekseenko, Zhanna Kee, Nigel Stanton, Lawrence W. Ericson, Johan Perlmann, Thomas School of Biological Sciences DRNTU::Science::Biological sciences::Cytology An important goal in stem cell biology is to develop methods for efficient generation of clinically interesting cell types from relevant stem cell populations. This is particularly challenging for different types of neurons of the central nervous system where hundreds of distinct neuronal cell types are generated during embryonic development. We previously used a strategy based on forced transcription factor expression in embryonic stem cell-derived neural progenitors to generate specific types of neurons, including dopamine and serotonin neurons. Here, we extend these studies and show that noradrenergic neurons can also be generated from pluripotent embryonic stem cells by forced expression of the homeobox transcription factor Phox2b under the signaling influence of fibroblast growth factor 8 (FGF8) and bone morphogenetic proteins. In neural progenitors exposed to FGF8 and sonic hedgehog both Phox2b and the related Phox2a instead promoted the generation of neurons with the characteristics of mid- and hindbrain motor neurons. The efficient generation of these neuron types enabled a comprehensive genome-wide gene expression analysis that provided further validation of the identity of generated cells. Moreover, we also demonstrate that the generated cell types are amenable to drug testing in vitro and we show that variants of the differentiation protocols can be applied to cultures of human pluripotent stem cells for the generation of human noradrenergic and visceral motor neurons. Thus, these studies provide a basis for characterization of yet an additional highly clinically relevant neuronal cell type. 2014-04-10T03:29:50Z 2019-12-06T21:00:45Z 2014-04-10T03:29:50Z 2019-12-06T21:00:45Z 2013 2013 Journal Article Mong, J., Panman, L., Alekseenko, Z., Kee, N., Stanton, L. W., Ericson, J., et al. (2014). Transcription factor-induced lineage programming of noradrenaline and motor neurons from embryonic stem cells. STEM CELLS, 32(3), 609-622. 1066-5099 https://hdl.handle.net/10356/102821 http://hdl.handle.net/10220/19210 10.1002/stem.1585 en Stem cells © 2013 AlphaMed Press. |
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DRNTU::Science::Biological sciences::Cytology Mong, Jamie Panman, Lia Alekseenko, Zhanna Kee, Nigel Stanton, Lawrence W. Ericson, Johan Perlmann, Thomas Transcription factor-induced lineage programming of noradrenaline and motor neurons from embryonic stem cells |
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An important goal in stem cell biology is to develop methods for efficient generation of clinically interesting cell types from relevant stem cell populations. This is particularly challenging for different types of neurons of the central nervous system where hundreds of distinct neuronal cell types are generated during embryonic development. We previously used a strategy based on forced transcription factor expression in embryonic stem cell-derived neural progenitors to generate specific types of neurons, including dopamine and serotonin neurons. Here, we extend these studies and show that noradrenergic neurons can also be generated from pluripotent embryonic stem cells by forced expression of the homeobox transcription factor Phox2b under the signaling influence of fibroblast growth factor 8 (FGF8) and bone morphogenetic proteins. In neural progenitors exposed to FGF8 and sonic hedgehog both Phox2b and the related Phox2a instead promoted the generation of neurons with the characteristics of mid- and hindbrain motor neurons. The efficient generation of these neuron types enabled a comprehensive genome-wide gene expression analysis that provided further validation of the identity of generated cells. Moreover, we also demonstrate that the generated cell types are amenable to drug testing in vitro and we show that variants of the differentiation protocols can be applied to cultures of human pluripotent stem cells for the generation of human noradrenergic and visceral motor neurons. Thus, these studies provide a basis for characterization of yet an additional highly clinically relevant neuronal cell type. |
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School of Biological Sciences |
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School of Biological Sciences Mong, Jamie Panman, Lia Alekseenko, Zhanna Kee, Nigel Stanton, Lawrence W. Ericson, Johan Perlmann, Thomas |
format |
Article |
author |
Mong, Jamie Panman, Lia Alekseenko, Zhanna Kee, Nigel Stanton, Lawrence W. Ericson, Johan Perlmann, Thomas |
author_sort |
Mong, Jamie |
title |
Transcription factor-induced lineage programming of noradrenaline and motor neurons from embryonic stem cells |
title_short |
Transcription factor-induced lineage programming of noradrenaline and motor neurons from embryonic stem cells |
title_full |
Transcription factor-induced lineage programming of noradrenaline and motor neurons from embryonic stem cells |
title_fullStr |
Transcription factor-induced lineage programming of noradrenaline and motor neurons from embryonic stem cells |
title_full_unstemmed |
Transcription factor-induced lineage programming of noradrenaline and motor neurons from embryonic stem cells |
title_sort |
transcription factor-induced lineage programming of noradrenaline and motor neurons from embryonic stem cells |
publishDate |
2014 |
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https://hdl.handle.net/10356/102821 http://hdl.handle.net/10220/19210 |
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1681038195718881280 |