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Advanced Modeling Effort Describes the Transcriptional Intricacies of Mouse Embryo Development

Review of “A single-embryo, single-cell time-resolved model for mouse gastrulation” from Cell by Stuart P. Atkinson

While advances in single-cell technologies have provided high-resolution descriptions of the transcriptional states of developing mouse embryos during gastrulation and organogenesis, using this data to understand collective cell dynamics remains a challenging prospect. In a recent study, researchers led by Amos Tanay and Yonatan Stelzer (Weizmann Institute of Science, Rehovot, Israel) sought to represent mammalian embryonic development as a continuous process by integrating single-cell RNA sequencing data from individual embryos with morphology to place them on a “continuum of transcriptional transformation” [1].

Mittnenzweig and Mayshar et al. developed a temporal model of mouse development from gastrulation to somitogenesis using data derived from their analyses of 153 E6.5–E8.25 embryos. From this new model, they inferred differentiation flows and lineage specification dynamics using algorithms that integrate single-embryo time, the transcriptional identity of single cells, and estimation of the growth rates for critical embryonic lineages [2].

Analysis of this model suggested that rapid transcriptional bifurcations characterized the commitment of some early specialized cells, including the cells of the node (a distinct structure arising from the anterior primitive streak that constitutes a major signaling center critical for the correct patterning of the embryo and determination of the left-right axis [3]) and blood progenitors. In these cases, the stepwise acquisition of transcriptional identity occurred through the hierarchical activity of fate-specific transcription factors; however, the authors discovered that these hierarchical transcriptional transitions represented relatively rare occurrences. Instead, most lineages displayed combinatorial multi-furcation dynamics, in that complex transcriptional dynamics in multipotent progenitor states and intricate combinatorial activity of transcription factors combine to drive multi-furcation events.

Overall, this fascinating new study provides evidence for an alternative quantitative model of cell fate acquisition that goes beyond differentiation as the simple consequence of a series of binary choices.

For more details on the ongoing efforts to faithfully model mouse gastrulation, stay tuned to the Stem Cells Portal!

References

  1. Mittnenzweig M, Mayshar Y, Cheng S, et al., A single-embryo, single-cell time-resolved model for mouse gastrulation. Cell 2021;184:2825-2842.e22.
  2. Ahuja RK, Magnanti TL, and Orlin JB, Network flows. 1988.
  3. Hirokawa N, Tanaka Y, Okada Y, et al., Nodal Flow and the Generation of Left-Right Asymmetry. Cell 2006;125:33-45.