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

The present [attached] article is an example of the incredible advances in technology (single-cell transcriptomics, in particular) that can now be performed in the field of developmental biology, and especially early-embryogenesis. The 48-hr period of mouse embryonic development — from embryonic day (E)6.5 to E8.5 (days after fertilization) — includes the key phases of gastrulation (early phase during embryogenesis in mammals, during which the single-layered blastula is reorganized into the multilayered gastrula) and early organogenesis (when organs begin to be formed), when pluripotent epiblast cells diversify into ectodermal, mesodermal and endodermal progenitors of all major organs [mouse embryos were dissected (at time-points E6.5, E6.75, E7.0, E7.25, E7.5, E7.75, E8.0, E8.25, and E8.5); development is known to proceed at different speeds between embryos — even in the same uterus — consequently, authors used ‘careful staging’ by morphology to exclude obvious outliers].

Although this period of mammalian development is known to be critically important, there has been a lack a comprehensive understanding of the underlying developmental trajectories and molecular processes involved — mainly because previous research efforts have used cell culture systems, or focused on small numbers of genes, or studied a small number of developmental stages or cell types. To investigate the dynamic process of cellular diversification during gastrulation and early organogenesis, authors [see attached article] generated single-cell RNA sequencing (scRNA-seq) profiles from 411 whole mouse embryos that had been collected at 6-hour intervals between E6.5 and E8.5; this dataset thus captures the time when there is enrichment of the pre-streak to early streak, mid-streak to late-streak, neural plate, and headfold to somitogenesis [somites are bilaterally paired blocks of mesoderm (on each side of the axis, running head-to-tail) in segmented animals; in animals with a spine — somites give rise to skeletal muscle, cartilage, tendons, endothelium, and dermis] stages.

The transcriptional profiles of 116,312 single cells from mouse embryos were collected at the nine sequential time-points. Authors constructed a molecular map of cellular differentiation from pluripotency (when embryonic stem cells are capable of giving rise to several different cell types) and head toward all major embryonic cell lineages. The complex events involved in convergence of visceral and primitive streak-derived endoderm were explored. Authors also used single-cell profiling to show that Tal1(−/−) chimeric embryos displayed defects in early-mesoderm diversification; these data demonstrate how combining temporal and transcriptional information can help us understand gene function.

Altogether, this AWESOME STUDY from Cambridge, UK — describing comprehensive delineation of mammalian cell differentiation trajectories in the developing mouse — represents a baseline for understanding the effects of gene mutations during development, as well as a roadmap for the optimization of differentiation protocols for regenerative medicine that might be studied in cell culture.


Nature Feb 2o19; 566 490-495

This entry was posted in Center for Environmental Genetics. Bookmark the permalink.