PUBLICATION
Single-cell chromatin accessibility maps reveal regulatory programs driving early mouse organogenesis
- Authors
- Pijuan-Sala, B., Wilson, N.K., Xia, J., Hou, X., Hannah, R.L., Kinston, S., Calero-Nieto, F.J., Poirion, O., Preissl, S., Liu, F., Göttgens, B.
- ID
- ZDB-PUB-200403-219
- Date
- 2020
- Source
- Nature cell biology 22(4): 487-497 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Cell Nucleus/genetics
- Cell Nucleus/metabolism
- Gene Expression Profiling
- Chromatin/chemistry*
- Chromatin/metabolism
- Mice, Transgenic
- Transcription Factors/genetics
- Transcription Factors/metabolism
- Enhancer Elements, Genetic*
- T-Cell Acute Lymphocytic Leukemia Protein 1/genetics*
- T-Cell Acute Lymphocytic Leukemia Protein 1/metabolism
- Embryo, Nonmammalian
- Protein Binding
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Gene Expression Regulation, Developmental*
- Endothelial Cells/cytology
- Endothelial Cells/metabolism*
- Animals
- Transcription, Genetic
- Organogenesis/genetics*
- Organ Specificity
- Embryonic Development
- Single-Cell Analysis
- Embryo, Mammalian
- Zebrafish
- Cell Lineage/genetics
- Mice
- PubMed
- 32231307 Full text @ Nat. Cell Biol.
Citation
Pijuan-Sala, B., Wilson, N.K., Xia, J., Hou, X., Hannah, R.L., Kinston, S., Calero-Nieto, F.J., Poirion, O., Preissl, S., Liu, F., Göttgens, B. (2020) Single-cell chromatin accessibility maps reveal regulatory programs driving early mouse organogenesis. Nature cell biology. 22(4):487-497.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping