Developmental and evolutionary dynamics of cis-regulatory elements in mouse cerebellar cells

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Authors list

Ioannis Sarropoulos Mari Sepp Robert Frömel Kevin Leiss Nils Trost Evgeny Leushkin Konstantin Okonechnikov Piyush Joshi Peter Giere Lena M Kutscher Margarida Cardoso Moreira Stefan M Pfister Henrik Kaessmann
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Abstract

Organ development is orchestrated by cell- and time-specific gene regulatory networks. In this study, we investigated the regulatory basis of mouse cerebellum development from early neurogenesis to adulthood. By acquiring snATAC-seq (single-nucleus assay for transposase accessible chromatin using sequencing) profiles for ~90,000 cells spanning 11 stages, we mapped cerebellar cell types and identified candidate cis-regulatory elements (CREs). We detected extensive spatiotemporal heterogeneity among progenitor cells and a gradual divergence in the regulatory programs of cerebellar neurons during differentiation. Comparisons to vertebrate genomes and snATAC-seq profiles for ∼20,000 cerebellar cells from the marsupial opossum revealed a shared decrease in CRE conservation during development and differentiation as well as differences in constraint between cell types. Our work delineates the developmental and evolutionary dynamics of gene regulation in cerebellar cells and provides insights into mammalian organ development.

Journal details

Journal Science
Volume 373
Issue number 6558
Pages eabg4696
Available online
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Publisher website (DOI) 10.1126/science.abg4696
Europe PubMed Central 34446581
Pubmed 34446581

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The publication was previously a preprint. View preprint