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

Authors
  • Sarropoulos, Ioannis1
  • Sepp, Mari1
  • Frömel, Robert1
  • Leiss, Kevin1
  • Trost, Nils1
  • Leushkin, Evgeny1
  • Okonechnikov, Konstantin2
  • Joshi, Piyush2
  • Giere, Peter3
  • Kutscher, Lena M.4
  • Cardoso-Moreira, Margarida1, 5
  • Pfister, Stefan M.2, 6
  • Kaessmann, Henrik1
  • 1 Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, D-69120 Heidelberg, Germany
  • 2 Hopp Children’s Cancer Center (KiTZ) Heidelberg, Division of Pediatric Neurooncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), D-69120, Heidelberg, Germany
  • 3 Museum für Naturkunde, Leibniz Institute for Evolution and Biodiversity Science, Berlin, Germany
  • 4 Hopp Children’s Cancer Center Heidelberg (KiTZ), Developmental Origins of Pediatric Cancer Group, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany
  • 5 Evolutionary Developmental Biology Laboratory, The Francis Crick Institute, London NW1 1AT, UK
  • 6 Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany
Type
Published Article
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Publication Date
Jul 29, 2021
Volume
373
Issue
6558
Identifiers
DOI: 10.1126/science.abg4696
PMID: 34446581
PMCID: PMC7611596
Source
PubMed Central
Disciplines
  • Article
License
Unknown

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 profiles for ~90,000 cells spanning eleven 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, but also 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.

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