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; AF Maarten Altelaar; Harold D. Macgillavry; Corette J. Wierenga; Casper C. Hoogenraad

doi:10.7554/ELIFE.58124

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, AF Maarten Altelaar, Harold D. Macgillavry, Corette J. Wierenga, Casper C. Hoogenraad

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

The differentiation of neuronal stem cells into polarized neurons is a well-coordinated process which has mostly been studied in classical non-human model systems, but to what extent these findings are recapitulated in human neurons remains unclear. To study neuronal polarization in human neurons, we cultured hiPSC-derived neurons, characterized early developmental stages, measured electrophysiological responses, and systematically profiled transcriptomic and proteomic dynamics during these steps. The neuron transcriptome and proteome shows extensive remodeling, with differential expression profiles of ~1100 transcripts and ~2200 proteins during neuronal differentiation and polarization. We also identified a distinct axon developmental stage marked by the relocation of axon initial segment proteins and increased microtubule remodeling from the distal (stage 3a) to the proximal (stage 3b) axon. This developmental transition coincides with action potential maturation. Our comprehensive characterization and quantitative map of transcriptome and proteome dynamics provides a solid framework for studying polarization in human neurons.

Original language	English
Article number	e58124
Pages (from-to)	1-25
Journal	eLife
Volume	9
DOIs	https://doi.org/10.7554/ELIFE.58124
Publication status	Published - 1 Sept 2020
Externally published	Yes

Funding

We thank Dr. Didier Trono for the lentiviral vector, and Nicky Scheefhals for her constructive feedback on the manuscript. This work was supported by the Netherlands Organization for Scientific Research (NWO-ALW-VICI, 865.10.010, CCH), the Netherlands Organization for Health Research and Development (ZonMW-TOP, 912.16.058, CCH), the European Research Council (ERC) (ERC-consolidator, 617050, CCH), and the research program of the Foundation for Fundamental Research on Matter (FOM, #16NEPH05, CJW).

Funders	Funder number
NWO-ALW-VICI	865.10.010
Netherlands Organization for Health Research and Development	912.16.058
Netherlands Organization for Scientific Research
Seventh Framework Programme	617050
Seventh Framework Programme
European Research Council
Stichting voor Fundamenteel Onderzoek der Materie
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Foundation for Fundamental Research on Matter	16NEPH05
Foundation for Fundamental Research on Matter

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title = "Quantitative mapping of transcriptome and proteome dynamics during polarization of human ipsc-derived neurons",

abstract = "The differentiation of neuronal stem cells into polarized neurons is a well-coordinated process which has mostly been studied in classical non-human model systems, but to what extent these findings are recapitulated in human neurons remains unclear. To study neuronal polarization in human neurons, we cultured hiPSC-derived neurons, characterized early developmental stages, measured electrophysiological responses, and systematically profiled transcriptomic and proteomic dynamics during these steps. The neuron transcriptome and proteome shows extensive remodeling, with differential expression profiles of ~1100 transcripts and ~2200 proteins during neuronal differentiation and polarization. We also identified a distinct axon developmental stage marked by the relocation of axon initial segment proteins and increased microtubule remodeling from the distal (stage 3a) to the proximal (stage 3b) axon. This developmental transition coincides with action potential maturation. Our comprehensive characterization and quantitative map of transcriptome and proteome dynamics provides a solid framework for studying polarization in human neurons.",

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AU - Lindhout, Feline W.

AU - Kooistra, Robbelien

AU - Portegies, Sybren

AU - Herstel, Lotte J.

AU - Stucchi, Riccardo

AU - Snoek, Basten L.

AU - Altelaar, AF Maarten

AU - Macgillavry, Harold D.

AU - Wierenga, Corette J.

AU - Hoogenraad, Casper C.

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

Abstract

Funding

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