Single-cell chromatin accessibility maps reveal regulatory programs driving early mouse organogenesis.
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Nature cell biology
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Pijuan-Sala, B., Wilson, N., Xia, J., Hou, X., Hannah, R., Kinston, S., Calero-Nieto, F. J., et al. (2020). Single-cell chromatin accessibility maps reveal regulatory programs driving early mouse organogenesis.. Nature cell biology, 22 (4), 487-497. https://doi.org/10.1038/s41556-020-0489-9
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-fertilisation. 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.
Cell Nucleus, Chromatin, Endothelial Cells, Embryo, Nonmammalian, Animals, Mice, Transgenic, Zebrafish, Mice, Zebrafish Proteins, Transcription Factors, Gene Expression Profiling, Organ Specificity, Transcription, Genetic, Gene Expression Regulation, Developmental, Protein Binding, Cell Lineage, Embryonic Development, Organogenesis, Embryo, Mammalian, Enhancer Elements, Genetic, Single-Cell Analysis, T-Cell Acute Lymphocytic Leukemia Protein 1
Wellcome Trust, Bloodwise, MRC, CRUK, NIH NIDDK
WELLCOME TRUST (105031/D/14/Z)
Cancer Research UK (21762)
National Institutes of Health (NIH) (via Pennsylvania State University) (R24DK106766)
Wellcome Trust (203151/Z/16/Z)
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External DOI: https://doi.org/10.1038/s41556-020-0489-9
This record's URL: https://www.repository.cam.ac.uk/handle/1810/303137
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