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

Nature
Blanca Pijuan-SalaBerthold Göttgens

Abstract

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.

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Datasets Mentioned

BETA
GSE87038

Methods Mentioned

BETA
scRNA-seq
flow cytometry
genotyping
fluorescence-activated cell sorting
FCS
dissection
transfection
chip

Software Mentioned

scran R package
DPT
Python
Cell Ranger
GSNAP
Gephi
destiny R package DiffusionMap
buildSNNGraph
DropletUtils
buildKNNGraph

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