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Modeling gene expression cascades during cell state transitions

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Rosebrock,  Daniel       
Transcriptional Regulation (Martin Vingron), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Vingron,  Martin       
Transcriptional Regulation (Martin Vingron), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Arndt,  Peter F.       
Evolutionary Genomics (Peter Arndt), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

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iScience_Rosebrock et al_2024.pdf
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Citation

Rosebrock, D., Vingron, M., & Arndt, P. F. (2024). Modeling gene expression cascades during cell state transitions. iScience, 27(4): 109386. doi:10.1016/j.isci.2024.109386.


Cite as: https://hdl.handle.net/21.11116/0000-000F-152F-6
Abstract
During cellular processes such as differentiation or response to external stimuli, cells exhibit dynamic changes in their gene expression profiles. Single-cell RNA sequencing (scRNA-seq) can be used to investigate these dynamic changes. To this end, cells are typically ordered along a pseudotemporal trajectory which recapitulates the progression of cells as they transition from one cell state to another. We infer transcriptional dynamics by modeling the gene expression profiles in pseudotemporally ordered cells using a Bayesian inference approach. This enables ordering genes along transcriptional cascades, estimating differences in the timing of gene expression dynamics, and deducing regulatory gene interactions. Here, we apply this approach to scRNA-seq datasets derived from mouse embryonic forebrain and pancreas samples. This analysis demonstrates the utility of the method to derive the ordering of gene dynamics and regulatory relationships critical for proper cellular differentiation and maturation across a variety of developmental contexts.