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Quantitative mapping of transcriptome and proteome dynamics during polarization of human iPSC-derived neurons

View ORCID ProfileFeline W. Lindhout, View ORCID ProfileRobbelien Kooistra, Sybren Portegies, Lotte J. Herstel, Riccardo Stucchi, Basten L. Snoek, Maarten Altelaar, Harold D. MacGillavry, Corette J. Wierenga, Casper C. Hoogenraad
doi: https://doi.org/10.1101/2020.04.21.052498
Feline W. Lindhout
1Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands
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  • ORCID record for Feline W. Lindhout
Robbelien Kooistra
1Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands
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  • ORCID record for Robbelien Kooistra
Sybren Portegies
1Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands
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Lotte J. Herstel
1Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands
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Riccardo Stucchi
1Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands
2Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CH Utrecht, The Netherlands
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Basten L. Snoek
3Theoretical Biology and Bioinformatics, Utrecht University, 3584 CH Utrecht, The Netherlands
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Maarten Altelaar
2Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CH Utrecht, The Netherlands
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Harold D. MacGillavry
1Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands
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Corette J. Wierenga
1Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands
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Casper C. Hoogenraad
1Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands
4Department of Neuroscience, Genentech, Inc, South San Francisco, CA 94080, USA
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  • For correspondence: c.hoogenraad@uu.nl
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ABSTRACT

Early neuronal development is a well-coordinated process in which neuronal stem cells differentiate into polarized neurons. This process has been well studied in classical non-human model systems, but to what extent this is recapitulated in human neurons remains unclear. To study neuronal polarization in human neurons, we cultured human iPSC-derived neurons, characterized early developmental stages, measured electrophysiological responses, and systematically profiled transcriptomic and proteomic dynamics during these steps. We found extensive remodeling of the neuron transcriptome and proteome, with altered mRNA expression of ~1,100 genes and different expression profiles of ~1,500 proteins during neuronal differentiation and polarization. We also identified a distinct stage in axon development marked by an increase in microtubule remodeling and apparent relocation of the axon initial segment from the distal to proximal axon. Our comprehensive characterization and quantitative map of transcriptome and proteome dynamics provides a solid framework for studying polarization in human neurons.

Competing Interest Statement

Casper Hoogenraad is an employee of Genentech, Inc., a member of the Roche group. The authors declare that they have no additional conflict of interest.

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  • * authors equally contributed

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Posted April 21, 2020.
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Quantitative mapping of transcriptome and proteome dynamics during polarization of human iPSC-derived neurons
Feline W. Lindhout, Robbelien Kooistra, Sybren Portegies, Lotte J. Herstel, Riccardo Stucchi, Basten L. Snoek, Maarten Altelaar, Harold D. MacGillavry, Corette J. Wierenga, Casper C. Hoogenraad
bioRxiv 2020.04.21.052498; doi: https://doi.org/10.1101/2020.04.21.052498
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Quantitative mapping of transcriptome and proteome dynamics during polarization of human iPSC-derived neurons
Feline W. Lindhout, Robbelien Kooistra, Sybren Portegies, Lotte J. Herstel, Riccardo Stucchi, Basten L. Snoek, Maarten Altelaar, Harold D. MacGillavry, Corette J. Wierenga, Casper C. Hoogenraad
bioRxiv 2020.04.21.052498; doi: https://doi.org/10.1101/2020.04.21.052498

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