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Single-cell chromatin accessibility maps reveal regulatory programs driving early mouse organogenesis.

Accepted version
Peer-reviewed

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Authors

Pijuan-Sala, Blanca  ORCID logo  https://orcid.org/0000-0003-0922-9111
Wilson, Nicola K 
Xia, Jun 
Hou, Xiaomeng 
Hannah, Rebecca L 

Abstract

During mouse embryonic development, pluripotent cells rapidly divide and diversify, yet the regulatory programs that define the cell repertoire for each organ remain ill-defined. To delineate comprehensive chromatin landscapes during early organogenesis, we mapped chromatin accessibility in 19,453 single nuclei from mouse embryos at 8.25 days post-fertilization. Identification of cell-type-specific regions of open chromatin pinpointed two TAL1-bound endothelial enhancers, which we validated using transgenic mouse assays. Integrated gene expression and transcription factor motif enrichment analyses highlighted cell-type-specific transcriptional regulators. Subsequent in vivo experiments in zebrafish revealed a role for the ETS factor FEV in endothelial identity downstream of ETV2 (Etsrp in zebrafish). Concerted in vivo validation experiments in mouse and zebrafish thus illustrate how single-cell open chromatin maps, representative of a mammalian embryo, provide access to the regulatory blueprint for mammalian organogenesis.

Description

Keywords

Animals, Cell Lineage, Cell Nucleus, Chromatin, Embryo, Mammalian, Embryo, Nonmammalian, Embryonic Development, Endothelial Cells, Enhancer Elements, Genetic, Gene Expression Profiling, Gene Expression Regulation, Developmental, Mice, Mice, Transgenic, Organ Specificity, Organogenesis, Protein Binding, Single-Cell Analysis, T-Cell Acute Lymphocytic Leukemia Protein 1, Transcription Factors, Transcription, Genetic, Zebrafish, Zebrafish Proteins

Journal Title

Nat Cell Biol

Conference Name

Journal ISSN

1465-7392
1476-4679

Volume Title

22

Publisher

Springer Science and Business Media LLC

Rights

All rights reserved
Sponsorship
Wellcome Trust (105031/D/14/Z)
Cancer Research UK (21762)
Medical Research Council (MR/S036113/1)
National Institute of Diabetes and Digestive and Kidney Diseases (R24DK106766)
Wellcome Trust (203151/Z/16/Z)
Medical Research Council (MC_PC_12009)
Wellcome Trust, Bloodwise, MRC, CRUK, NIH NIDDK