Waves of early transcriptional activation and pluripotency program initiation during human preimplantation development

TLDR

Human preimplantation development remains poorly understood because of limited material, ethical constraints, and inadequate single‑cell transcriptome amplification, yet it is gaining renewed interest for its links to stem cell biology, epigenetic reprogramming, and regenerative medicine. The authors created HumER, a public database cataloging human preimplantation gene expression to support research. Genome‑wide single‑cell transcriptomics revealed successive waves of transcription beginning at the 2‑cell stage and a hierarchical activation of pluripotency genes, linking early embryonic transcription to proper pluripotency program execution and offering targets to enhance epigenetic reprogramming.

Abstract

The events regulating human preimplantation development are still largely unknown owing to a scarcity of material, ethical and legal limitations and a lack of reliable techniques to faithfully amplify the transcriptome of a single cell. Nonetheless, human embryology is gathering renewed interest due to its close relationship with both stem cell biology and epigenetic reprogramming to pluripotency and their importance in regenerative medicine. Carefully timed genome-wide transcript analyses of single oocytes and embryos uncovered a series of successive waves of embryonic transcriptional initiation that start as early as the 2-cell stage. In addition, we identified the hierarchical activation of genes involved in the regulation of pluripotency. Finally, we developed HumER, a database of human preimplantation gene expression, to serve the scientific community. Importantly, our work links early transcription in the human embryo with the correct execution of the pluripotency program later in development and paves the way for the identification of factors to improve epigenetic reprogramming.