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Dynamics and consequences of widespread transcript isoform changes during neuronal differentiation

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE245325 | GEO | 2024/04/10

REPOSITORIES: GEO

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Dynamics and consequences of widespread transcript isoform changes during neuronal differentiation

Project description:Static gene expression programs have been extensively characterized in stem cells and mature human cells. However, the dynamics of RNA isoform change upon cell-state transitions during cell differentiation, and the determinants and functional consequences have largely remained unclear. Here, we used an improved model for human neurogenesis in vitro that we show is amenable for systems-wide analyses of gene expression. Our multi-omics analysis reveals that the pronounced alterations in cell morphology correlate strongly with widespread changes in RNA isoform expression. Our approach identifies thousands of new RNA isoforms that are expressed at distinct stages during neurogenesis. RNA isoforms mainly arise from the alternative usage of transcription start sites and poly-adenylation sites as well as the skipping of individual exons during human neurogenesis. The transcript isoform changes can remodel the abundance and functions of protein isoforms. Finally, our study identifies a set of RNA-binding proteins as a likely determinant of differentiation stage-specific global isoform changes.

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