Journal Article

A single-cell molecular map of mouse gastrulation and early organogenesis

Tyser, Richard C. V., Reik, Wolf, Srinivas, Shankar, Göttgens, Berthold, Ibarra-Soria, Ximena, Mulas, Carla, Griffiths, Jonathan A., Calero-Nieto, Fernando J., Jawaid, Wajid, Marioni, John C., Ho, Debbie Lee Lian, Guibentif, Carolina, Hiscock, Tom W., Pijuan-Sala, Blanca, Nichols, Jennifer, Simons, Benjamin D.

2019

Overview

Across the animal kingdom, gastrulation represents a key developmental event during which embryonic pluripotent cells diversify into lineage-specific precursors that will generate the adult organism. Here we report the transcriptional profiles of 116,312 single cells from mouse embryos collected at nine sequential time points ranging from 6.5 to 8.5 days post-fertilization. We construct a molecular map of cellular differentiation from pluripotency towards all major embryonic lineages, and explore the complex events involved in the convergence of visceral and primitive streak-derived endoderm. Furthermore, we use single-cell profiling to show that Tal1 −/− chimeric embryos display defects in early mesoderm diversification, and we thus demonstrate how combining temporal and transcriptional information can illuminate gene function. Together, this comprehensive delineation of mammalian cell differentiation trajectories in vivo represents a baseline for understanding the effects of gene mutations during development, as well as a roadmap for the optimization of in vitro differentiation protocols for regenerative medicine. Single-cell profiling is used to create a molecular-level atlas of cell differentiation trajectories during gastrulation and early organogenesis in the mouse.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13 / 13/31 / 38 / 38/91 / 631/114/2397 / 631/136/1455 / 631/337/2019 / 64 / 64/60 / Animals / Bioinformatics / Cell differentiation / Cell Differentiation - genetics / Cell Lineage - genetics / Cells (Biology) / Chimera - embryology / Chimera - genetics / Chimera - metabolism / Criminal investigation / Cytological research / Developmental biology / Differentiation (biology) / Diversification / Embryo, Mammalian - cytology / Embryo, Mammalian - metabolism / Embryonic development / Embryos / Endoderm / Endoderm - cytology / Endoderm - embryology / Endoderm - metabolism / Endothelium - cytology / Endothelium - embryology / Endothelium - metabolism / Female / Fertilization / Gastrulation / Gastrulation - genetics / Gene expression / Gene Expression Profiling / Gene Expression Regulation, Developmental - genetics / Gene mutation / Genes / Genomes / Hematopoiesis - genetics / Humanities and Social Sciences / Kinases / Male / Mesoderm / Mesoderm - cytology / Mesoderm - embryology / Mice / multidisciplinary / Mutation / Mutation - genetics / Myeloid Cells - cytology / Optimization / Organogenesis / Organogenesis - genetics / Pluripotency / Pluripotent Stem Cells - cytology / Pluripotent Stem Cells - metabolism / Primitive streak / Primitive Streak - cytology / Primitive Streak - embryology / Regenerative medicine / Science / Science (multidisciplinary) / Single-Cell Analysis / Stem cell research / Stem cells / T-Cell Acute Lymphocytic Leukemia Protein 1 - deficiency / T-Cell Acute Lymphocytic Leukemia Protein 1 - genetics / Transcription / Transcription (Genetics)