Proteomics

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


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.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Stem Cell, Cell Culture

DISEASE(S): Disease Free

SUBMITTER: Robbelien Kooistra  

LAB HEAD: Casper Hoogenraad

PROVIDER: PXD020227 | Pride | 2020-11-17

REPOSITORIES: Pride

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

Lindhout Feline W FW   Kooistra Robbelien R   Portegies Sybren S   Herstel Lotte J LJ   Stucchi Riccardo R   Snoek Basten L BL   Altelaar Af Maarten AM   MacGillavry Harold D HD   Wierenga Corette J CJ   Hoogenraad Casper C CC  

eLife 20200917


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 step  ...[more]

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