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

Autor:	Ha KCH; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, M5S 3E1, Canada.; Department of Molecular Genetics, University of Toronto, Toronto, ON, M5A 1A8, Canada.; Vector Institute, Toronto, ON, M5G 1M1, Canada.; BioSymetrics, Inc., Huntington, New York, NY, USA., Sterne-Weiler T; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, M5S 3E1, Canada., Morris Q; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, M5S 3E1, Canada.; Department of Molecular Genetics, University of Toronto, Toronto, ON, M5A 1A8, Canada.; Vector Institute, Toronto, ON, M5G 1M1, Canada.; Department of Computer Science, University of Toronto, Toronto, ON, M5S 4G4, Canada., Weatheritt RJ; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, M5S 3E1, Canada. r.weatheritt@garvan.org.au.; EMBL Australia, Garvan Institute of Medical Research, Darlinghurst, NSW, 2010, Australia. r.weatheritt@garvan.org.au.; St. Vincent Clinical School, University of New South Wales, Darlinghurst, NSW, 2010, Australia. r.weatheritt@garvan.org.au., Blencowe BJ; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, M5S 3E1, Canada. b.blencowe@utoronto.ca.; Department of Molecular Genetics, University of Toronto, Toronto, ON, M5A 1A8, Canada. b.blencowe@utoronto.ca.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2021 Jan 12; Vol. 12 (1), pp. 335. Date of Electronic Publication: 2021 Jan 12.
DOI:	10.1038/s41467-020-20483-8
Abstrakt:	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.
Databáze:	MEDLINE
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