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Differential contribution of transcriptomic regulatory layers in the definition of neuronal identity


Previous transcriptomic profiling studies have typically focused on separately analyzing mRNA expression, alternative splicing and alternative polyadenylation differences between cell and tissue types. However, the relative contribution of these three transcriptomic regulatory layers to cell type specification is poorly understood. This question is particularly relevant to neurons, given their extensive heterogeneity associated with brain location, morphology and function. In the present study, we generated profiles for the three regulatory layers from developmentally and regionally distinct subpopulations of neurons from the mouse hippocampus and broader nervous system. Multi-omics factor analyses revealed differing contributions of each transcriptomic layer in the discrimination of neurons based on their stage of development, region, and function. Importantly, profiles of differential alternative splicing and polyadenylation better discriminated specific neuronal subtype populations than gene expression patterns. These results provide evidence for differential relative contributions of coordinated gene regulatory layers in the specification of neuronal subtypes.

Type Journal
ISBN 2041-1723 (Electronic) 2041-1723 (Linking)
Authors Ha, K. C. H.; Sterne-Weiler, T.; Morris, Q.; Weatheritt, R. J.; Blencowe, B. J.
Responsible Garvan Author A/Prof Robert Weatheritt
Publisher Name Nature Communications
Published Date 2021-01-31
Published Volume 12
Published Issue 1
Published Pages 335
Status Published in-print
DOI 10.1038/s41467-020-20483-8
URL link to publisher's version