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

Autor: Sarropoulos I; Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, D-69120 Heidelberg, Germany. h.kaessmann@zmbh.uni-heidelberg.de s.pfister@dkfz.de i.sarropoulos@zmbh.uni-heidelberg.de m.sepp@zmbh.uni-heidelberg.de., Sepp M; Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, D-69120 Heidelberg, Germany. h.kaessmann@zmbh.uni-heidelberg.de s.pfister@dkfz.de i.sarropoulos@zmbh.uni-heidelberg.de m.sepp@zmbh.uni-heidelberg.de., Frömel R; Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, D-69120 Heidelberg, Germany., Leiss K; Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, D-69120 Heidelberg, Germany., Trost N; Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, D-69120 Heidelberg, Germany., Leushkin E; Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, D-69120 Heidelberg, Germany., Okonechnikov K; 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., Joshi P; 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., Giere P; Museum für Naturkunde, Leibniz Institute for Evolution and Biodiversity Science, Berlin, Germany., Kutscher LM; Hopp Children's Cancer Center (KiTZ) Heidelberg, Developmental Origins of Pediatric Cancer Group, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany., Cardoso-Moreira M; Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, D-69120 Heidelberg, Germany.; Evolutionary Developmental Biology Laboratory, Francis Crick Institute, London NW1 1AT, UK., Pfister SM; 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. h.kaessmann@zmbh.uni-heidelberg.de s.pfister@dkfz.de i.sarropoulos@zmbh.uni-heidelberg.de m.sepp@zmbh.uni-heidelberg.de.; Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany., Kaessmann H; Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, D-69120 Heidelberg, Germany. h.kaessmann@zmbh.uni-heidelberg.de s.pfister@dkfz.de i.sarropoulos@zmbh.uni-heidelberg.de m.sepp@zmbh.uni-heidelberg.de.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2021 Aug 27; Vol. 373 (6558). Date of Electronic Publication: 2021 Jul 29.
DOI: 10.1126/science.abg4696
Abstrakt: 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.
(Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze: MEDLINE
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