A Comprehensive Human Embryogenesis Reference Tool using Single-Cell RNA-Sequencing Data

Abstract

Stem cell-based embryo models offer unprecedented experimental tools for studying early human development. The usefulness of embryo models hinges on their molecular, cellular and structural fidelities to their in vivo counterparts. To authenticate human embryo models, single-cell RNA-sequencing has been utilised for unbiased transcriptional profiling. However, a well-organised and integrated human single-cell RNA-sequencing dataset, serving as a universal reference for benchmarking human embryo models, remains unavailable. Herein, we developed such a reference, through integration of six published human datasets covering developmental stages from the zygote to the gastrula. Lineage annotations are contrasted and validated with available human and non-human primate datasets. Using stabilised UMAP we constructed a web tool, where query datasets can be projected on the reference and annotated with predicted cell identities. Using this reference tool, we examined several recent human embryo models, highlighting the risk of misannotation when relevant references are lacking.