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All-defined NGN2 neuron protocol reveals multifaceted signatures of neuronal maturation [scRNA-seq]

ABSTRACT: All-defined NGN2 neuron protocol reveals multifaceted signatures of neuronal maturation [scRNA-seq]

PROVIDER: PRJNA1022484 | ENA |

REPOSITORIES: ENA

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All-defined NGN2 neuron protocol reveals multifaceted signatures of neuronal maturation.

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Project description:Direct conversion of iPSCs into neurons by NGN2 over-expression is a popular method for disease modeling. Here we report a standardized method to generate functional excitatory cortical neurons using clonal, targeted engineered iPSC lines and defined reagents. We demonstrate that our protocol generates consistent excitatory cortical neurons at scale. These cultures can be maintained healthily for at least 150 days and expresses the majority of the GWAS genes found in autism, Parkinson’s disease, and Alzheimer’s disease. Comprehensive temporal omics, functional, and morphological profiling demonstrated continued progression of neuronal maturation. Deep functional characterization through transcriptomic, imaging, and functional assays revealed the coordinated action of multiple pathways in neuronal maturation. Our method and profiling data can serve as reference for developing human in vitro neuronal models for disease modeling.

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Project description:NGN2-driven iPSC-to-neuron conversion is a popular method for human neurological disease modeling. In this study, we report a fully standardized approach for generating functional excitatory cortical neurons. This method utilizes clonal, targeted-engineered iPSC lines and employs fully defined reagents. We demonstrate that our protocol generates consistent excitatory cortical neurons at scale. Comprehensive temporal omics, electrophysiological, and morphological profilings indicate the continued progression of neuronal maturation for at least 150 days. Deep quantitative characterizations through transcriptomic, imaging, and functional assays reveal coordinated actions of multiple pathways driving neuronal maturation. The neurons express the majority of the key risk genes in Alzheimer's disease, Parkinson's disease, and autism, demonstrating the relevance of our protocol in modeling human neurological disorders. This well-defined method, profiling data, and functional characterization provide a solid and reliable framework for developing human in vitro neuronal models for disease modeling.

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Project description:This SuperSeries is composed of the SubSeries listed below.

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