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A multiscale model via single-cell transcriptomics reveals robust patterning mechanisms during early mammalian embryo development

What is being modeled?
Early mammalian embryo development
Description & purpose of resource

During early mammalian embryo development, a small number of cells make robust fate decisions at particular spatial locations in a tight time window to form inner cell mass (ICM), and later epiblast (Epi) and primitive endoderm (PE). While recent single-cell transcriptomics data allows scrutinization of heterogeneity of individual cells, consistent spatial and temporal mechanisms the early embryo utilize to robustly form the Epi/PE layers from ICM remain elusive. Here we build a multiscale three-dimensional model for mammalian embryo to recapitulate the observed patterning process from zygote to late blastocyst. By integrating the spatiotemporal information reconstructed from multiple single-cell transcriptomic datasets, the data-informed modeling analysis suggests two major processes critical to the formation of Epi/PE layers: a selective cell-cell adhesion mechanism (via EphA4/EphrinB2) for fate-location coordination and a temporal attenuation mechanism of cell signaling (via Fgf). Spatial imaging data and distinct subsets of single-cell gene expression data are then used to validate the predictions. Together, our study provides a multiscale framework that incorporates single-cell gene expression datasets to analyze gene regulations, cell-cell communications, and physical interactions among cells in complex geometries at single-cell resolution, with direct application to late-stage development of embryogenesis.

Spatial scales
whole organism
Temporal scales
This resource is currently
mature and useful in ongoing research
Has this resource been validated?
How has the resource been validated?

The model results are validated by in vivo image data and supported by scRNA-seq data.

Key publications (e.g. describing or using resource)

Zixuan Cang*, Yangyang Wang*, Qixuan Wang, Ken WY Cho, William Holmes, and Qing Nie. "A multiscale model via single-cell transcriptomics reveals robust patterning mechanisms during early mammalian embryo development." PLOS Computational Biology 17, no. 3 (2021): e1008571.

Qing Nie (PI)
PI contact information
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Model type