Defining cell lineages by single-cell RNA-Seq

Researchers at the Francis Crick Institute provide fundamental insights into early human development by single-cell RNA-sequencing of human and mouse preimplantation embryos. They elucidate conserved transcriptional programs along with those that are human-specific and validate their RNA-sequencing findings at the protein level. They identified several genes exclusively expressed in the human pluripotent epiblast including the transcription factor KLF17. Intriguingly, inhibition of TGF-β signaling abrogates NANOG expression in human epiblast cells, consistent with a requirement for this pathway in pluripotency. Comparisons of the human epiblast to existing embryonic stem cells (hESCs) reveals conservation of pluripotency but also additional pathways more enriched in hESCs. This analysis highlights significant differences in human preimplantation development compared to mouse and provides a molecular blueprint to understand human embryogenesis and its relationship to stem cells.
Cytoscape enrichment map of GSEA results comparing human TE (blue) versus EPI (red), and mouse TE (blue) versus ICM (red) (p-value < 0.01)